Bone turnover, osteopenia and vascular calcifications in hemodialysis patients. A histomorphometric and multislice CT study.

BACKGROUND: Several classical risk factors are at the base of vascular calcifications in hemodialysis patients. Among these, according to a general opinion, also bone turnover plays a role, which, however, requires a better definition. In addition, it has been suggested that there is a relationship between primary osteoporosis and vascular calcifications. This bone biopsy-based study on a hemodialysis patient cohort is a contribution to the evaluation of these alleged relations. METHODS: This study has been carried out on a cohort of 32 patients on maintenance hemodialysis, who were subjected to transiliac bone biopsy for histomorphometric, histodynamic and bone aluminum deposit evaluation. The patients were also examined with multislice computerized tomography for quantitation of heart and coronary calcifications. RESULTS: The patients were affected by renal osteodystrophy with a wide range of bone formation rate values. A significant negative correlation was found between the rate of bone turnover and log-transformed cardiac calcification score (p < 0.003). There were also negative significant correlations between the cardiac and coronary calcification score log and trabecular number (p < 0.02 and p < 0.05, respectively), while the correlations were positive with trabecular separation (p < 0.03 and p < 0.05, respectively). However, multiregression analysis, forward method, selected only age, hemodialysis age and serum Ca as predictive variables of cardiac and coronary calcification score log, while the histomorphometric and histodynamic variables were excluded. CONCLUSIONS: In this study, in spite of the suggestive findings of the univariate statistical approach, a further multivariate analysis was indicative of a spurious association between calcification scores and both bone turnover and histomorphometric parameters of trabecular mass and connectivity. Bone turnover and trabecular mass do not appear to be prominently connected with the extent of cardiac and coronary calcifications in hemodialysis patients.

Active coating and modified-atmosphere packaging to extend the shelf life of Fior di Latte cheese.

In this work the combination of active coating and modified-atmosphere packaging (MAP) was used to prolong the shelf life of Fior di Latte cheese. The active coating was based on sodium alginate (8% wt/vol) containing lysozyme (0.25 mg/mL) and EDTA, disodium salt (Na(2)-EDTA, 50 mM). The MAP was made up of 30% CO(2), 5% O(2), and 65% N(2). The speed of quality loss for the Fior di Latte cheese, stored at 10 degrees C, was assessed by monitoring pH and weight loss, as well as microbiological and sensorial changes. Results showed that the combination of active coating and MAP improved Fior di Latte cheese preservation, increasing the shelf life to more than 3 d. In addition, the substitution of brine with coating could allow us to gain a double advantage: both preserving the product quality and reducing the cost of its distribution, due to the lower weight of the package.

Shelf life of Stracciatella cheese under modified-atmosphere packaging.

The aim of this work is to evaluate the shelf life of Stracciatella cheese packaged in a protective atmosphere, using 4 different CO(2):N(2):O(2) gas mixtures [50:50:0 (M1), 95:5:0 (M2), 75:25:0 (M3), and 30:65:5 (M4) vol/vol] and stored at 8 degrees C. Cheese in traditional tubs and under vacuum were used as the controls. Results showed that the modified-atmosphere packaging, in particular M1 and M2, delayed microbial growth of spoilage bacteria, without affecting the dairy microflora, and prolonged the sensorial acceptability limit.

[Cytomegalovirus and BK polyomavirus infection after renal transplantation]. / Infezione da citomegalovirus (CMV) e da polioma BK virus (BKV) dopo trapianto di rene.

Cytomegalovirus (CMV) and BK polyomavirus (BKV) infections have been described in a high percentage of renal transplant patients and are known to cause various complications in renal transplantation. They are closely related to immunosuppressive therapy and implicated in the progression of graft failure. This review focuses on the clinical aspects of CMV and BKV infection after renal transplantation, optimal monitoring, and recent preventive measures and interventions to improve graft function and recipient survival.

Effects of natural compounds on microbial safety and sensory quality of Fior di Latte cheese, a typical Italian cheese.

This work presents a preliminary study to assess the efficiency of plant essential oils as natural food preservatives in Fior di Latte cheese. Selected compounds were directly dissolved into Fior di Latte brine. Packaged Fior di Latte samples were stored at 10 degrees C for about 6 d. The cell loads of spoilage and useful microorganisms were monitored to calculate the microbial acceptability limit. Results show that some tested compounds were not acceptable by the panel from a sensorial point of view. Most compounds did not affect the microbial acceptability limit value to a great extent, and only a few such as lemon, sage, and thyme markedly prolonged the microbial acceptability limit of the investigated fresh cheese. Moreover, the above active agents exerted an inhibitory effect on the microorganisms responsible for spoilage without affecting the dairy microflora.

Effect of chitosan on the rheological and sensorial characteristics of Apulia spreadable cheese.

The effect of chitosan on the rheological and sensorial properties of Apulia spreadable cheese during storage time was evaluated. The investigated spreadable cheese samples were stored at 4 degrees C. Storage modulus (G'), loss modulus (G''), tandelta, and the overall sensorial quality of the spreadable cheese were monitored for 24 d. Moreover, moisture content, pH, color, and lactic acid bacteria during storage time were evaluated. Results indicate that statistically significant differences in G', G'', and tandelta values and in the sensorial scores exist between the control sample and the spreadable cheese samples with chitosan. In particular, chitosan improved the rheological and sensorial properties of the spreadable cheese, particularly its softness. Moreover, its addition influenced the physicochemical properties of the investigated spreadable cheese during storage time, without affecting the dairy microflora.

[Update of the Italian Society of Nephrology Project No. 1 of the 2004-2006 SIN programme]. / Update sul progetto SIN n. 1 del programma SIN 2004-2006: qualità e accreditamento delle strutture di nefrologia, dialisi e trapianto.

In the last few years the Italian Society of Nephrology has addressed many technical-scientific and management aspects to better patient satisfaction. Project No. 1 of the 2004-2006 programme on 'Quality and Accreditation of National Renal Units' focuses on four essential points. The first is the questionnaire mailed to all the Presidents and Regional Delegates on the relationship between Nephrology units, Local Government Health-System and the Regional Healthcare Agency. The results evidence that the 'political' decision-making power of nephrologists decreases in the absence of a national strategy. The second point, in collaboration with the National Census Group, includes the quality analysis and the standardization of resources (human and structural) and management of the Renal Units. The third point is based on 'Educational Courses for Quality and Accreditation' held in Rome (3-5 October 2005: L'Accreditamento all'Eccellenza dell'Unita' Operativa di Nefrologia, Dialisi e Trapianto; 17-19 October 2005: Il Manuale di Accreditamento della Specialità di Nefrologia). The courses aim at training members responsible for each region to hold courses in their specific region to create a network including each single Renal Unit to create an acceptable homogenous language on the models of analysis and on the correct use of 'The Guide for Excellence Accreditation'. The fourth point concerns both the on-line Guide for Excellence Accreditation and 'Peer Review Accreditation' and the NEQUASY (Nephrology Quality System) project. The manual must be 'user friendly' allowing each Centre to self-evaluate using national and regional standards.

Expanded Criteria Donor Kidney Transplantation: Comparative Outcome Evaluation Between Single Versus Double Kidney Transplantation at 8 Years: A Single Center Experience.

Transplantation of kidneys retrieved from expanded criteria donors is one of the options to expand the pool of available grafts, shorten the waiting time and increase the number of kidney transplant recipients. This study was a retrospective assessment of 99 patients who underwent renal transplantation during the period 2007-2015 with kidneys harvested from expanded criteria donors (ECD) as defined by the United Network for Organ Sharing (UNOS) following routine biopsy of all kidneys obtained by Karpinsky Score. They formed two groups: SKT (67 recipients that received a single kidney) and DKT (32 patients that received dual kidney transplant). An analysis of differences of two groups between graft and patient survival and graft function were performed after 8 years of observation. We observed between two groups the following statistical differences: Donor age (P < .001), basal high risk of recipients (P < .05), wait time before transplant (P < .05), recipient age (P < .001) delayed graft function (P < .005) while we observe similar values of donor renal function, outcome in graft and patient survival and graft function in recipients. The transplantation of kidneys obtained from expanded criteria donor, allows increase in the number of kidney transplants and in the respect of values of biopsy score and the donor renal function, showed in single or dual kidney transplantation with similar graft and patient survival.

Stimulated platelets release factor(s) affecting the in vitro response of human polymorphonuclear cells.

The metabolic and functional responses of human polymorphonuclear cells (PMNs) to thrombin-activated platelet supernatants were studied. The incubation of PMNs with supernatants from stimulated platelets (SPS) caused a 50% decrease in both killing of Staphylococcus aureus and luminol-enhanced chemiluminescence (CL) by PMNs stimulated by opsonized-zymosan (OZ), Concanavalin A (Con A), or calcium ionophore A23187. The levels of PMN intracellular fluorescence measured by flow cytometry, using the fluorochrome dichlorofluorescein diacetate (DCF-DA), were considerably less in the presence of SPS than in resting platelet supernatants (RPS). No influence of platelet supernatant on O2 consumption and O2- generation by OZ-activated PMNs was observed. The incubation of PMNs with SPS caused a significant increase in the rate of chemotaxis and aggregation elicited by Con A, OZ, and phorbol myristate acetate (PMA). The supernatant from resting platelets did not show any of the above-reported effects. Platelets previously degranulated by thrombin were unable to inhibit CL when activated with agonists. Studies on the differential release of the granules by platelets showed that the CL-quenching activity paralleled the discharge of lysosomal content. The release of myeloperoxidase (MPO) from PMNs elicited by OZ was reduced in the presence of SPS. The platelet supernatant did not affect the MPO activity if PMNs were lysed with Triton X-100. The leakage of lactate dehydrogenase (LDH) from platelets was less than 3%, and no catalase or superoxide dismutase was released. This activity withstood lyophilization, but was destroyed by 10 min heating at 100 degrees C or by treatment with proteolytic enzymes.

A surface NAD-glycohydrolase of human platelets may influence their aggregation.

Human platelets may hydrolyze externally added NAD+ yielding ADPR and nicotinamide. The extent of hydrolysis is significantly higher when the platelets are stimulated. The presence of external NAD+ strongly inhibits the aggregation induced by every agonist used. It seems that adenosine or ADPR itself generated by NAD+ hydrolysis may be responsible for the inhibition of aggregation. Evidence is given that some of the NAD+ hydrolysis product is taken up by stimulated platelets.

Hydrogen peroxide has a role in the aggregation of human platelets.

The aggregation of platelets induced by soluble and particulate stimuli is enhanced by the addition of minute amounts of H2O2. Externally added catalase strongly inhibits the aggregation induced by particulate stimuli and by phorbol myristate acetate (PMA). The addition of aminotriazole to stimulated platelets causes a significant inhibition of intracellular catalase. This indicates the formation of H2O2 inside the platelets during activation. No effects were observed when the platelets were stimulated by the ionophore A23187.

Livedo vasculopathy vs small vessel cutaneous vasculitis: cytokine and platelet P-selectin studies.

OBJECTIVE: To assess the role of platelets and lymphocyte-related immunological mechanisms in livedo vasculopathy (LV) and cutaneous small vessel vasculitis (CSVV). Livedo vasculopathy is thought to be related to the thrombotic occlusion of small and medium-sized dermal vessels. Cutaneous small vessel vasculitis comprises a heterogeneous group of disorders in which the main pathogenetic events could be modulated by circulating cytokines. DESIGN: Case series study of 2 groups of patients affected respectively with LV and CSVV. SETTING: A large clinical and research institute for the study and treatment of cutaneous diseases. PATIENTS: Consecutive patients with clinically and histologically proved idiopathic LV (n = 8) and CSVV (n = 20) were studied and compared with healthy donors (n = 20). Patients with potentially correlated systemic diseases were excluded. MAIN OUTCOME MEASURES: Surface expression of platelet P-selectin and circulating level of interleukin (IL) 1beta, tumor necrosis factor alpha (TNF-alpha), IL-8, IL-2, and soluble IL-2 receptor. RESULTS: The IL-2 and soluble IL-2 receptor levels were significantly higher in serum samples from patients with both LV (1.24 +/- 0.46 IU/mL [mean +/- SD] vs 0.46 +/- 0.24 IU/mL, P<.001; 899 +/- 368 IU/mL vs 628 +/- 132 IU/mL, P<.02) and CSVV (0.91 +/- 0.57 IU/mL, P<.02; 1087 +/- 451 IU/mL, P<.001) than in those from the healthy controls. The serum levels of IL-1beta, TNF-alpha, and IL-8 were higher in patients with CSVV than in controls (7.53 +/- 6.7 pg/mL vs 4.58 +/- 2.72 pg/mL; 23.7 +/- 12.6 pg/mL vs 10.82 +/- 2.46 pg/mL, P<.001; 37.8 +/- 46 pg/mL vs 8.25 +/- 3.53 pg/mL, P<.02, respectively). No significant difference in the serum levels of IL-1beta (7.2 +/- 4.9 pg/mL), TNF-alpha (12.9 +/- 3.47 pg/mL), and IL-8 (5.9 +/- 4.13 pg/mL) was observed in patients with LV compared with controls. An increased expression of platelet P-selectin was also detected in patients with LV in comparison with controls and patients with CSVV. The mean +/- SD percentage of positive cells for P-selectin was 43% +/- 5% in the patients with LV, 5.1% +/- 2% in the controls (P<.001), and 5.3% +/- 2% in the patients with CSVV (P<.001). CONCLUSIONS: Taken together, these data demonstrate that different pathogenetic mechanisms are operative in LV and CSVV. In fact, platelet and lymphocyte activation is present in LV, whereas the levels of inflammatory mediators are in a normal range. In CSVV, the high serum levels of proinflammatory cytokines suggest that they are actively involved in the pathogenesis of cutaneous vasculitis.

Hydrogen peroxide is an intermediate in the platelet activation cascade triggered by collagen, but not by thrombin.

Human blood platelets produce oxidant species when stimulated by collagen and thrombin. The oxidative burst of platelets has been studied by cytofluorimetry taking advantage of the fluorogenic dye DCFH2-DA, which is taken up and deacetylated by platelets and then oxidized to the fluorescent derivative DCF. The oxidation of DCFH2 is induced by stimulation with collagen but not with thrombin and inhibited by external catalase. Catalase also inhibited the aggregation induced by collagen, but not that induced by thrombin. Aspirin and indomethacin inhibited the formation of the fluorochrome only when platelets were stimulated by thrombin. Externally added H2O2 increased the cytoplasmic calcium content as probed by the fluorescence of Indo-1. The present data suggest that collagen induces the production of H2O2, which in turn may stimulate the aggregation of platelets through a calcium mobilization. Instead the stimulation by thrombin does not require the intermediacy of H2O2.

Risk management of HBsAg or anti-HCV positive healthcare workers in hospital.

Recommendations are made for controlling the transmission of the hepatitis B and hepatitis C viruses from healthcare workers to patients. These recommendations were based both on the literature and on experts' opinions, obtained during a Consensus Conference. The quality of the published information and of the experts' opinions was classified into 6 levels, based on the source of the information. The recommendations can be summarised as follows: all healthcare workers must undergo hepatitis B virus vaccination and adopt the standard measures for infection control in hospitals; healthcare workers who directly perform invasive procedures must undergo serological testing and the evaluation of markers of viral infection. Those found to be positive for: 1) HBsAg and HBeAg, 2) HBsAg and hepatitis B virus DNA, or 3) anti-hepatitis C virus and hepatitis C virus RNA must abstain from directly performing invasive procedures; no other limitations in their activities are necessary. Infected healthcare workers are urged to inform their patients of their infectious status, although this is left to the discretion of the healthcare worker; whose privacy is guaranteed by law. If exposure to hepatitis B virus occurs, the healthcare worker must undergo prophylaxis with specific immunoglobulins, in addition to vaccination.

Possible persistent endocrine function of a rejected renal allograft.

The case is described of a patient on intermittent hemodialysis who had had a bilateral nephrectomy but had hypertension and a surprisingly mild degree of anemia. Repeated determinations showed high plasma renin activity and plasma erythropoietin activity within the detectable range. These results were thought to be related to a completely calcified renal allograft which had been inserted 8 years before and which had been rejected four years later, but left in situ. The patient had become anuric. It is suggested that chronically rejected renal allografts, even calcified, may maintain some endocrine activity in the absence of any excretory function.

Aluminium-induced, reversible microcytic anemia in chronic renal failure: clinical and experimental studies.

Ten chronic hemodialysis patients with severe aluminium (Al) intoxication developed a microcytic anemia despite oral iron supplementation. Their microcytosis was reversible after deionization of the dialysis water. Ten age and sex matched hemodialysis patients who were not Al intoxicated but who had a comparable treatment schedule and time on dialysis had no such microcytosis. In order to investigate a possible direct role of Al we intoxicated uremic rats by daily (6/7 days a week) intraperitoneal injections of 30 nmoles/day of aluminium. After 3 months, the Al-intoxicated uremic rats had a significantly lower hematocrit (34.7%), hemoglobin (12.0 g/dl), and MCV (52.5 fl) than the control, vehicle-injected uremic animals (37.4%, 13.1 g/dl and 60.4 fl., respectively). The reticulocyte counts of the intoxicated rats were increased. Serum iron and transferrin iron binding capacity were unchanged. Thus aluminium intoxication of the uremic organism leads to a microcytic anemia possibly by interfering directly with normal hemoglobin synthesis.

Clofibrate treatment of hyperlipidemia in chronic renal failure.

The pharmacokinetics of the hypolipidemic agent, clofibrate have been studied in anuric patients on intermittent hemodialysis. In addition we have tried to determine whether the treatment of hyperlipidemia of chronic renal failure with clofibrate was safe and efficacious. Seven healthy volunteers and five uremic patients received a single dose of 25 mg/kg body weight of clofibrate. Mean peak plasma levels of clofibrate were comparable in both groups and were reached 3.5 hr after drug ingestion in the control subjects and after 6.5 hr in the uremic patients. The mean plasma half-life of clofibrate was 16.7 hr and 68.4 hr in the control subjects and in the patients, respectively (P less than 0.001). Following a short loading period a daily oral maintenance dose of 5 mg/kg body weight was given leading to a plasma clofibrate level of 75-100 microgram/100 ml. Five hyperlipidemic uremic patients received this dose for 3 months. Their plasma clofibrate and creatine kinase levels were constantly monitoried to detect clofibrate myotoxicity which we have observed in uremic patients at plasma levels generally considered safe in patients with normal renal function. Significant decreases in serum total lipid, triglyceride, and cholesterol levels were observed when compared to pretreatment values. In two of the 5 patients serum lipids remained decreased for 10 and 14 months. It is concluded that clofibrate treatment of hyperlipidemia in uremic patients, when carefully monitored, is safe and efficacious.

Reasons for producing guidelines on anemia of chronic renal failure: dialysis outcome quality initiative of the National Kidney Foundation.

Guidelines for the treatment of anemia in chronic renal failure (CRF) patients were recently published by NKF-DOQI. The background was provided by the fact that anemia in CRF patients fulfills all the criteria requested for the outlining of guidelines. In fact: 1) anemia is a clinically relevant problem for CRF patients; 2) it may be prevented by adequate erythropoietin (EPO) therapy; 3) a great variability in its management exists, not only concerning the optimal hematocrit (HCT) level, but also the treatment schedule as well as iron supplementation. More than eight hundred forty five scientific articles were retrieved in full text, eventually leading to 530 structurally reviewed papers (349 cited in the final text) thus providing the basis for the strength of recommendations (evidence or opinions): all topics were subdivided into 7 main issues (diagnostic and therapeutic). Main results were the following: HCT, hemoglobin (Hb), red blood cell, serum iron binding capacity, percent transferrin saturation (TSAT) and serum ferritin (FERR), to evaluate the degree of anemia and iron status; HCT 33 to 36% and Hb 11 to 12 g/dl as possible target levels; TSAT >20% and FERR >100 ug/dl as acceptable lower values for iron status; oral iron administration not <200 mg/day of elemental iron and intravenous iron 50-100 mg/week or 500-100 mg/month (for patients on predialysis or peritoneal dialysis) as therapeutic schedules; subcutaneous route for EPO administration at 80-120 U/kg body weight/week as starting doses. Some issues may be debatable, such as, the underestimation of dialysis efficacy among the causes of inadequate response to EPO as well as the risk of thrombosis among the possible side effects of EPO therapy, or the lack of recommendation for upper limits of FERR values. However, this exhaustive study is an important demonstration of efforts to improve the quality of care in CRF patients.

Dialysis outcome quality initiative (DOQI) guideline for hemodialysis adequacy.

The article about Dialysis Outcome Quality Initiative (DOQI), recently published by the National Kidney Foundation in The American Journal of Kidney Disease provides clear guidelines for adequacy of hemodialysis, peritoneal dialysis, vascular access and treatment of anemia in End-Stage Renal Disease (ESRD). If the dissemination of these guidelines actually increases Kt/V, an early improvement of the outcome of dialysis patients will be expected because there is a close correlation between dialysis dose and mortality. Mortality, unless high, is the main indicator of the efficacy of guidelines in ESRD. Other indicators are needed to assess the effects of the modification in clinical practice induced by DOQI at lower mortality, as in other western European countries. Quality of life adjusted for life expectancy defined Kt/V of 1.3 as the optimal cost-effective dialysis dose; large evidence is missing to support the use of higher doses or of high technology in hemodialysis treatment. Adequacy and uniformity of isolated hemodialysis procedures are accurately defined by DOQI. Quality assessment of integrated actions in overall commitment of ESRD patients (prevention and treatment of co-morbidity of uremia, renal transplantation programs, improvement of the communication with caregivers and family, enhanced fitness and ability to work) has still to be implemented with recommendations and indicators of the outcome. NKF-DOQI defined only dialysis adequacy; further work is necessary to assess the "optimal clinical practice" for ESRD patients.

[Epidemiology and prevention in dialysis]. / Epidemiologia e prevenzione in emodialisi.

During the last years, prevention of hospital infections assumed the role of primary objective for active interventions and dedicated laws for safety in work areas and for facilities accreditation defined responsibilities and preventive measures to reduce the biological risk. Dialysis centers are areas where the infective risk is high but the strict application of the Universal Measures and of specific recommendations are sufficient to reduce the risk of diffusion and transmission of pathogens. The late referral of the ESRD patient, with or without infectious comorbidity, shows an intervention field, in which a local epidemiological survey gives useful data and stimulates the data management at hospital level (Epidemiologists and nefrologists) and family doctors, to improve the disease management of very complex and high cost patients.