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Despite the clear cost, ease of installation, and construction schedule advantages of confinement of concrete structural elements with fibre-reinforced polymers (FRPs) for strength and deformability enhancement, concerns as to their performance at elevated temperature, or in fire, remain. The results of a series of elevated temperature experiments on FRP and textile reinforced mortar (TRM) strengthening systems for confinement of circular concrete columns are presented. The behaviour and effectiveness of the respective confining systems is studied up to temperatures of 400 °C. A total of 24 concrete cylinders were wrapped in the hoop direction with different amounts of FRP or TRM, heated to steady-state temperatures between 20 and 400 °C, and loaded to failure in concentric axial compression under a steady-state thermal regime. The results indicate that the effectiveness of the FRP confining system bonded with epoxy decreased considerably, but did not vanish, with increasing temperatures, in particular within the region of the glass transition temperature of the epoxy resin/adhesive. Conversely, the TRM confining system, bonded with inorganic mortar rather than epoxy, demonstrated superior performance than the FRP confining system at 400 °C as compared against tests performed at ambient temperature.

Textile reinforced mortar (TRM) is a promising alternative to the FRP retrofitting solution for shear strengthening of reinforced concrete (RC) beams, based on the experimental results presented so far in the literature. Thus, the development of reliable and accurate design models for shear strengthening of concrete members with TRM is required for enabling their wider use in real applications. The available experimental data in the literature are limited and in most cases, a detailed description of the failure modes observed in the TRM jackets and information related to the characteristics of the textile material and the mortar strength are missing, complicating the development of design guidelines. In this paper, a design model to calculate the contribution of the TRM jacket to the total shear resistance was developed using all the well reported available data that were grouped based on the observed failure modes. Specifically, local damage of the jacket including slippage of the fibres through the mortar constitutes a recurring failure mode in concrete beams strengthened in shear with TRM jackets, apart from debonding of the jacket from the concrete substrate including peeling-off of the concrete cover or fracture of TRM jacketing that are also observed in case of fibre reinforced polymer (FRP) jacketing. The key parameters affecting each failure mode were defined and design formulations to calculate the contribution of the TRM jacket to the total shear resistance of RC beams for each failure mode were suggested, whereas a criterion indicating when each failure mode is possible to be observed was also set for using the proper formulation for each TRM system.

Textile reinforced mortars (TRM), also known in the international literature as textile reinforced concrete (TRC) or fabric reinforced cementitious matrix (FRCM) materials, have been widel...

This paper presents an experimental study on shear strengthening of rectangular reinforced concrete (RC) beams with advanced composite materials. Key parameters of this study include: (a) the strengthening system, namely textile-reinforced mortar (TRM) jacketing and fiber-reinforced polymer (FRP) jacketing, (b) the strengthening configuration, namely side-bonding, U-wrapping and full-wrapping, and (c) the number of the strengthening layers. In total, 14 RC beams were constructed and tested under bending loading. One of the beams did not receive any strengthening and served as control beam, eight received TRM jacketing, whereas the rest five received FRP jacketing. It is concluded that the TRM is generally less effective than FRP in increasing the shear capacity of concrete, however the effectiveness depends on both the strengthening configuration and the number of layers. U-wrapping strengthening configuration is much more effective than side-bonding in case of TRM jackets and the effectiveness of TRM jackets increases considerably with increasing the number of layers.

This paper presents the first study on the performance of TRM and FRP jacketing in shear strengthening of reinforced concrete (RC) members subjected to ambient and high temperatures, including both medium-scale rectangular beams and full-scale T-beams. Key parameters investigated on the medium-scale rectangular RC beams include: (a) the matrix used to impregnate the fibres, namely resin or mortar, resulting in two strengthening systems (TRM or FRP), (b) the level of high temperature to which the specimens are exposed (20 °C, 100 °C, 150 °C, 250 °C), (c) the strengthening configuration (side-bonding, U-wrapping and full-wrapping), (d) the number of jacketing layers (2 and 3) and (e) the textile properties (geometry, material). The effectiveness of both non-anchored and anchored TRM jackets in shear strengthening of full-scale T-beams at high temperature was also studied. It is concluded that TRM possess excellent performance as strengthening material at high temperature. TRM jacketing remained very effective in shear strengthening of concrete at high temperature; on the contrary the effectiveness of side-bonding and U-wrapping FRP jacketing was reduced nearly to zero when subjected at temperatures above the glass transition temperature.

Post hoc test comparison. Table S2. On multivariate Cox regression, the daily cumulative fluid was a predictor of mortality for only the Overall population and AKI patients. After adjusted analysis N-AKI patients were not independently associated with a higher risk of death, even with a higher mean cumulative fluid overload. Table S3. FO (%) on ICU discharge for Alive and Death patients. FO (%) for All patients, N-AKI, AKI and AKI-RRT for survivors and non-survivors. (DOCX 19Â kb)

Scores displayed as a pie chart. Figure S2. Fluid balance chart. The red dot represents the diuretics while the area under the curve is the cumulative fluid. The green and blue lines are respectively the total intake and the urine output. (DOCX 250Â kb)

Adsorption may notably contribute to the removal of uremic toxins and to the efficiency of hemodialysis. We examined different uncoated stationary matrixes, charcoals and synthetic resins to establish their adsorptive capacities in relation to low (urea, creatinine) and high molecular weight (β2-microglobulin, myoglobin) compounds in in vitro conditions (steady state and flow-through) using isotonic solutions or uremic ultrafiltrate. Trace metal, particle release analyses and scanning electron microscopy of different adsorbents were performed. Dynamic flow-distribution studies were made using 99Technetium and analysing the different regions of interest by single head γ-camera. We show that adsorbents may differ greatly as to their adsorptive capacity depending on flow rate, nature, and total mass of the compounds to be removed from the ultrafiltrate. These studies suggest a methodological approach for screening stationary matrixes for possible application in hemodialysis.

Base-line serum levels of plasma C-reactive protein (CRP) are predictive of future myocardial infarction and sudden cardiac death in apparently healthy subjects, suggesting the hypothesis that chronic inflammation might be important in the pathogenesis of atherothrombosis. CRP production is mediated by several inflammatory mediators: interleukin 6 (IL-6) is currently felt to be the major cytokine influencing the acute phase response. CRP and other acute phase proteins are elevated in dialysis patients and cardiovascular diseases represent the single largest cause of mortality in chronic renal failure patients. Little information is available, however regarding CRP and IL-6 plasma levels in pre-dialysis renal failure. Plasma CRP was determined by a modification of the laser nephelometry technique; IL-6 by immunoassay (RD System); and fibrinogen, serum albumin, cholesterol, triglycerides, hematocrit, white blood cell count, erythrocytic sedimentation rate (ESR) and urinary protein levels by standard laboratory techniques. Results were obtained in 102 chronic pre-dialysis patients whose mean age was 53+/-5.8 years with a mean creatinine clearance (C(Cr)) of 52+/-37 mL/min). CRP was greater than 5 mg/L in 25% of the global population. CRP and IL-6 were 4.0+/-4.6 mg/L and 5.8+/-5.6 pg/mL, respectively and were not significantly correlated (r=0.11, p=n.s.). CRP and IL-6 were however related with renal function (CRP versus C(Cr) r=-0.40 p

Applicazioni dell'ecografia nella patologia del rene e nel trapianto renale

In hemodialysis patients, C-reactive protein (CRP), an acute-phase reactant, is a sensitive and independent marker of malnutrition, anemia, and amyloidosis. The aim of the present studies was to evaluate CRP and interleukin 6 levels in plasma samples from long-term hemodialysis patients on different extracorporeal modalities associated with or without backfiltration. Two hundred and forty-seven patients were recruited in eight hospital-based centers. All patients had been on their dialytic modality for at least 6 months. At enrollment, 46 hemodialysis patients out of 247 (18.6%) had clinical evidence of pathologies known to be associated with high CRP values. The 201 remaining patients were defined as clinically stable and were on conventional hemodialysis (34%), hemodiafiltration with infusion volumes 20 liters/session, in hemodialysis and in double-chamber hemodiafiltration. The same pattern occurred after 6 months of follow-up in 171 out of 201 clinically stable patients. Hemodialytic conditions that expose to the risk of backfiltration such as low exchange volume hemodiafiltration may induce a chronic inflammatory state as reflected by increased plasma values of both CRP and interleukin 6, thus suggesting the need for hemodialytic strategies that reduce (hemodialysis with low-permeability membranes or hemodiafiltration with infusion volumes >20 liters) or eliminate (double-chamber hemodiafiltration) backfiltration of bacteria-derived contaminants.

Haemodialysis is associated with increased oxidant stress. This appears to be due to (1) an increased production of free radicals during haemodialysis, (2) a net reduction of many antioxidants and (3) factors intrinsic to the uremic state. These alterations can lead to cardiovascular disease and many of the pathologies associated with chronic renal failure. Haemolipodialysis (HLD) is a new haemodialytic technique aimed at reducing oxidant stress and removing hydrophobic or protein bound toxins. The technique uses dialysate containing ascorbic acid (vitamin C) and polyunsaturated unilamellar liposomes containing α-tocopherol (vitamin E). The liposomes interact with blood components at the haemodialysis membrane without passage through the membrane. Vitamin C and vitamin E are added to the system to protect the cell and plasma components from reactive oxygen species produced from activated inflammatory cells. This technique may provide a new approach in preventing free radical-associated pathologies in chronic haemodialysis patients.

Background: Several studies have suggested that uremic toxins may adversely affect phagocytic leukocytes of chronic renal failure patients. Platelet-activating factor (PAF) is produced by phagocytic leukocytes and is a potent mediator of inflammation which is produced by leukocytes upon appropriate stimulation. Methods: We added uremic or normal ultrafiltrate, ultrafiltrate fractionated by reverse phase HPLC or compounds eluting at the same retention time as the fractionated ultrafiltrate, to normal leukocytes. Complement-coated baker’s yeast spores were added to stimulate phagocytosis. Total PAF was purified by thin layer chromatography and quantified by bioassay on rabbit platelets. The activities of two enzymes involved in the synthesis of PAF, phospholipase A2 (PLA2) and acetyltransferase, were measured in the presence of fractionated ultrafiltrate. Results: Ultrafiltrate from both healthy and uremic subjects inhibited PAF synthesis, but the inhibitory effect was more substantial for uremic subjects. Ultrafiltrate fractionated by HPLC showed high PAF inhibition for late eluting hydrophobic fractions. Addition of phenol or p-cresol, two uremic toxins with similar elution pattern as the late fractions, also inhibited PAF synthesis. The activity of PLA2 and acetyltransferase was decreased in the presence of uremic ultrafiltrate. Conclusions: We observed that uremic ultrafiltrate inhibits PAF synthesis upon stimulation with complement coated baker’s yeast spores. The decrease in total PAF synthesis appears to be associated with an inhibition of phospholipase A2 and acetyltransferase activity, enzymes involved in the remodelling pathway for PAF synthesis.

Calcitriol modulates in vivoand in vitro cytokine production: A role for intracellular calcium. Background. Several immunomodulatory properties of calcitriol are currently known, however, only little information is available regarding the in vivo and in vitro effects of calcitriol on cytokine production in chronic renal failure. Methods. To study the in vitro effect of calcitriol on lipopolysaccharide (LPS)-induced cytokine production, peripheral blood mononuclear cells (PBMC, 2.5 ml/ml) from 12 chronic dialytic (HD), 15 undialyzed chronic renal failure (CRF) patients and 10 normal subjects (N) were incubated at 37 degrees for 12 hours with 100 ng of LPS (E. coli and P. maltofilia). Increasing doses of calcitriol from 10-10 to 10-9 M were added and cell associated TNF-alpha and IL-1beta were determined by immunoreactive tests after three freeze-thaw cycles. The intradialytic TNF-alpha and IL-1beta production were evaluated in vivo in 12 HD patients before and after three months of intravenous calcitriol treatment (6 microgram/week). Intracellular calcium [Ca++]i was determined on PBMC with a cytofluorimetric assay using FLUO-3 AM as the indicator. Results. In vitro, TNF-alpha increased from 3.6 +/- 1.9 pg/cell to 1797 +/- 337 in N, from 4.5 +/- 1.7 to 1724 +/- 232 in CRF and from 3.4 +/- 2.3 to 1244 +/- 553 in HD after the LPS stimulus. The production of TNF-alpha was inhibited by calcitriol in a dose-dependent manner [LPS + Vit.D3 100 ng, 2.9 +/- 2.1 in N, 3.7 +/- 1.9 in CRF and 3.4 +/- 1.7 in HD; LPS + Vit.D3 50 ng, 263 +/- 296 (N), 6.73 +/- 11 (CRF), 38 +/- 28 (HD); LPS + Vit.D3 25 ng = 873 +/- 583 (N), 325 +/- 483 (CRF), 588 +/- 507 (HD); LPS + Vit.D3 12.5 ng, 954 +/- 483 (N), 912 +/- 510 (CRF), 875 +/- 527 (HD)]. Comparable data were observed on IL-1beta production. In vivo, the intradialytic TNF-alpha increase (from 8.5 +/- 2.3 to 19 +/- 5.6 pg/2.5 x 106 cell) during hemodialysis was markedly reduced after calcitriol therapy (from 6.6 +/- 3.1 to 11 +/- 4.7). [Ca++]i decreased from 105 +/- 25 to 72 +/- 18 nM (P < 0.05) and a positive correlation between cytokine levels and [Ca++]i was found (r = 0.79; P < 0.001). Conclusions. The in vitro increase of cell-associated cytokine after LPS challenge was inhibited by calcitriol in a dose-dependent manner. These data suggest a possible in vivo modulatory effect of calcitriol therapy on cytokine production in hemodialysis.

Regenerated cellulosic membranes are held as bioincompatible due to their high complement - and leukopenia - inducing properties. Adherence of polymorphonuclear neutrophils and monocyte purified from normal human blood to the three membranes were evaluated in an in vitro recirculation circuit in the presence or absence of fresh, autologous plasma after recirculation in an in vitro circuit using minimodules with each of the three membranes. In in vivo studies, 9 patients were treated with conventional haemodialysis for 2 weeks with each membrane and 1 week for wash-out using haemodialysers with the following surface: 1.95 m2for benzyl-cellulose, 1.8 m2for acetate-cellulose and low-flux polysulfone. Measurement of leukopenia, plasma C3a des Arg and elastase-α 1 proteinase inhibitor complex levels as well as urea, creatinine, phosphate and uric acid clearances was performed. Plasma-free neutrophils adhered maximally to acetate-cellulose (65% remaining in the circulation), while there was no significant difference between low-flux polysulfone and benzyl-cellulose (80% circulating neutrophils, at 15 min, p

Since the initial description of the use of continuous arteriovenous hemofiltration (CAVH) in the critically ill [1], continuous renal replacement therapy (CRRT) has steadily evolved from an adjuvant therapy for acute renal failure (ARF) to a well-established, widely used, fully independent form of artificial kidney support [2]. This evolution has taken place because of the shortcomings of standard, intermittent hemodialysis in the treatment of an increasingly large population of severely ill multiorgan failure patients. It has also taken place because the technology (the “hardware”) supporting the application of CRRT has improved and because the medical understanding of the potential of this therapy has greatly expanded. This chapter will describe this evolution of CRRT, and it will focus on where the “search for the best” might take this therapy in the next few years.

Critically ill patients are increasingly being treated with continuous haemofiltration and its derived techniques, now grouped under the term 'continuous renal replacement therapies' (CRRT). CRRT can provide adequate blood purification and correction of electrolyte derangements. They also seem to prevent further injury to the patient by maintaining a stable level of homoeostasis. Recently, it has been proposed that CRRT could be used in the treatment of neonates, of patients with heart disease and, finally, of septic patients. It has been hypothesised that continuous therapies might contribute to the removal of noxious substances in the middle molecular weight range such as cytokines or autacoids. According to these new proposals, technical developments are making available new forms of treatment, new materials and specially designed machines.

We tested a new biosensor for urea monitoring in the ultrafiltrate during PFD in a group of 5 hemodialyzed stable patients. The inspection of the UF-urea profile reflects the dynamical changes of the plasma urea concentration during diffusive dialysis and allows the fitting of the main mathematical models of urea kinetics. The biosensor efficiency was 98.4% on average (SD: 1.5%) at Uf fluxes varying from 45 to 55 ml/min (mean: 51 ml/min; SD: 3.2) and at Uf-urea concentrations varying from 23 to 165 mg/dl. The mean difference between Uf-urea determined by the laboratory method and Uf-urea assayed by the biosensor was -1.07 mg/dl and the 95% confidence interval ranged from -2.01 to 0.13 mg/dl. The mean difference between laboratory plasma urea and Uf-urea from the biosensor was on average -1.9 mg/dl and the estimated limits of agreement with a confidence of 95% were -3.16 and 0.64 mg/dl. Comparison between kinetic models and experimental profiles of plasma urea decrease, evaluations of recirculation and post-dialytic rebound, the role of Kt/V on-line during dialysis were the preliminary clinical applications of this biosensor.

Autonomic dysfunction in patients with end- stage renal disease is associated with poor prognosis. Heart rate variability (HRV), determined by the standard deviation of the normal R- R interval, has been reported to be a useful evaluation of cardiac autonomic modulation. The relationship between HRV and hydration status (HS) can be analyzed by whole body bioimpedance spectroscopy. This allows a classification of patients according the combination of HS with predialysis systolic blood pressure. Differences in HRV can be studied in patients with high over hydration, but normal or low blood pressure, with respect to fluid-overloaded/hypertensive patients and normohydrated/normotensive patients. In conclusion, the assessment of the autonomic nervous system response to the hemodialysis treatment in end- stage renal disease patients, classified according to a reliable and quantitative measurement of their fluid overload, could permit better management of both arterial blood pressure and HS.

We tested in vivo the effect of methyl-prednisolone (MP) on C5a release and granulocytopenia occurring early in the course of extracorporeal blood circulation through a Cuprophan dialyzer. MP boluses (30 mg/kg) were given to 10 consenting patients suffering from acute renal failure, immediately before blood started to circulate through a hollow-fiber Cuprophan dialyzer. To avoid drug loss through the dialyzer membrane, dialysate flow was witheld during the first hour of treatment and ultrafiltration was kept near zero (sham dialysis). Control procedures were carried out in a similar way, without MP. MP concentration, differential WBC count and anaphylotoxin C5a were serially measured during the procedures. MP pharmacokinetics was evaluated in six other uremic patients off dialysis. As shown by similar C5a levels in dialyzer effluent blood, complement cascade was activated by Cuprophan to a comparable degree whether or not patients received MP. Neutrophil count dropped 68% during the control procedure and 54% during sham dialysis preceded by MP (95% confidence interval of the difference, 1.97–27.2). Sham dialysis did not apparently influence serum MP levels, as shown by similar peak values in patients undergoing sham dialysis (203 μg/ml ± SEM 33) and in patients off dialysis (177 μg/ml ± 42). In vitro aggregometry showed that the uremic milieu does not interfere with the antiaggregating effect of MP. Our results show that MP at the dosage of 30 mg/kg does not affect complement-mediated granulocytopenia in any important way.

The biologic response to uremia and to the associated chronic inflammation is an active area of research. Among the different modalities developed in the technology field of chronic renal replacement, hemodialfiltration has evolved consistently. On-line production of substitution fluid by 'cold sterilization' of dialysis fluid by ultrafiltration gives access to virtually an unlimited amount of sterile and non-pyrogenic intravenous grade solution. Today, on line HDF is already a widespread, accepted treatment. Here, we will review the main mechanisms through which on line hemodialfiltration acts and the biological response observed in relation to the immune system dysfunction and the anemia associated to chronic kidney disease.

The purpose of this study was to evaluate the differential diagnosis of pulmonary nodules by conventional radiography and computed tomography (CT) in osteosarcoma patients with central venous catheter. Between March 1997 and December 2001 at our Department of Musculoskeletal Oncology, 231 patients with peripheral osteosarcoma received a central venous catheter to allow infusion therapy and blood sampling. The mean age of these patients was 16 years (range 4–63), and 90 were aged 15 years or younger. All patients underwent radiological investigation for tumour staging and comparison with the following study in accordance with the protocol in place at our Department of Oncology and Division of Diagnostic Imaging. Of a total of 231 patients, 13 (5.6%) developed an infection of the central venous line, with fever that was very high in some cases. In ten cases (4.3%), radiology showed damage to the alveolar interstitium typical of inflammatory forms, whereas in the remaining three (1.3%) it depicted nodular opacities, which required differentiation between lung metastases and septic emboli. After appropriate antibiotic and replacement of the central venous line, CT demonstrated disappearance of the lung nodules in all three patients, enabling a diagnosis of nodular septic embolism. Placement of a central venous catheter for infusion therapy, chemotherapy and blood sampling has improved the quality of life of cancer patients. The most common complications of the use of central venous catheters include infection and venous thrombosis whereas pulmonary septic emboli are rare.

Chronic inflammation has been repeatedly reported in individuals undergoing hemodialysis. C-reactive protein (CRP) is considered a marker of chronic inflammation, as well as a mediator of the atherosclerotic process. Clinical and epidemiologic studies are based on plasma values obtained with the use of various automated methods. Our aim was to test 3 commercially available methods and compare the values obtained with the use of these tests in a population of individuals undergoing hemodialysis. We compared the following methods: immunoturbidimetry (AU2700 biochemistry analyzer; Olympus, Rungis, France) laser nephelometry (Behring Diagnostics, Marburg, Germany), and nephelometry (Beckman Instruments, Fullerton, Calif. The 3 methods were used in 3 different centers: Montpellier, France; and Pisa and Turin, Italy, respectively. We prepared samples for the estimation of imprecision values (ie, coefficient of variation [CV]) from the plasma of normal patients by adding purified C-reactive protein at concentrations ranging from 2.6 to 180 mg/L for intraassay variation and concentrations of 0, 1, 2, 3, 5, 10, 20, 50, 100, 150, and 180 mg/L for interassay variation. Intraassay imprecision was determined with the use of 10 replicate analyses on the same sample of the same day. We assessed interassay imprecision using the same sample, divided into aliquots and measured on 5 consecutive days. Agreement between methods was assessed on predialysis serum samples collected from patients with stable chronic kidney disease who were undergoing long-term hemodialysis at the 3 different centers (Montpellier,192; Pisa, 56; Turin,98). Serum was separated from the red cells and stored in 3 aliquots at -70 degrees C until it could be analyzed. Samples were thawed only once, circulated among the 3 centers, and each tested with all 3 of the methods. The Beckman method yielded the most precise results, with intraassay CVs ranging from 1 to 2 and interassay CVs ranging from 1 to 4. The Behring method was the least precise, with intraassay and interassay CVs ranging from 12 to 15 and 7 to 16, respectively. The results of the Olympus method fell between those of the other 2 methods. Agreement between the results of the Olympus and Behring methods was satisfactorily. The Beckman and Olympus methods yielded, on average, similar results over the entire range of CRP values. We detected significant disagreement between the Beckman method and the other 2 methods, obtaining results 10 to 100 times lower with the Beckman method. This became evident in terms of kappa-statistics. Our findings emphasize the need for careful assessment of the methods used to detect CRP in serum samples. Failure to do so may ultimately have a negative impact on the real relevance of CRP as a marker and on the role of chronic implication particularly in epidemiologic studies.

The study of cell reaction to micro and nanotopography is dependent on the method of manufacture available. Several methods of manufacture have been developed: polymer demixing, embossing and photolithography. Surfaces obtained with these different techniques, having micro and/or nanodomains, have been studied toward the same type of cells, i.e. human endothelial cells (HGTFN) and mouse fibroblasts (3T3). Polymer demixing of polystyrene (PS) and poly(4-bromostyrene) (PBrS) producing nanometrically islands of 18, 45 and 100 nm height, polycarbonate (PC) and polycaprolactone (PCL) grooved with grooves 450 nm wide and 190 high, the natural polysaccharide hyaluronic acid (Hyal) and its sulfated derivative (HyalS) photoimmobilized on silanized glass as grooves 250 nm high and 100, 50, 25 or 10 microm wide have been obtained. The morphology and polarization of the cells has been studied by optical microscopy and scanning electron microscopy. Cells respond in different way to the topography of the materials, but the surface chemistry is dominant in inducing different cell behavior.

Acute renal failure (ARF) is increasingly seen as part of the multiple organ dysfunction syndrome (MODS) in critically ill patients [1,2]. MODS is the most-frequent cause of death in patients admitted to intensive care units [3]. Severe sepsis and septic shock are the primary causes of MODS [4, 5] and develop as a result of the host response to infection of Gram-negative and Gram-positive bacteria [6]. Infectious sepsis and non-infectious systemic inflammatory response syndrome (SIRS) encompass a complex mosaic of interconnected events. Molecules such as bacterial lipopolysaccharides (LPS), microbial lipopeptides, microbial DNA, peptidoglycan and lipoteichoic acid trigger interact with the Toll-like receptors and related molecules (MD-2, MyD88), the principal sensors of the innate immune response [7–9]. Stimulus-receptor coupling activates different signal transduction pathways, leading to exacerbated generation of cytokines, and phospholipase A2-dependent, arachidonic acid-derived platelet-activating factor (PAF), leukotrienes, and thromboxanes. At the plasma level, activation of the complement (C3a, C5a, and their desarginated products) and coagulation pathways interacts with the process, as products generated in the fluid phase may in turn trigger and sustain cell activation. Other agents play a role in the pathophysiology of sepsis, such as surface-expressed and soluble adhesion molecules, kinins, thrombin, myocardial depressant substance(s), endorphin, and heat shock proteins.

Acute renal failure is increasingly seen as part of the multiple organ dysfunction syndrome (MODS) in critically ill patients [1, 2]. MODS is the most frequent cause of death in patients admitted to intensive care units (ICUs) [3]. Severe sepsis and septic shock are the primary causes of MODS [4, 5] and develop as a result of the host response to infection by Gram-negative and Gram-positive bacteria [6]. Sepsis encompasses a complex mosaic of interconnected events. Molecules such as bacterial lipopolysaccharides (LPS), microbial lipopeptides, microbial DNA, peptidoglycan and lipoteichoic acid interact with the Toll-like receptors (TLR) and related molecules (MD-2, MyD88), the principal sensors of the innate immune response [7–9]. Stimulus-receptor coupling activates different signal transduction pathways leading to exacerbated generation of cytokines, and phospholipase A2-dependent, arachidonic acid-derived platelet-activating factor (PAF), leukotrienes, and thromboxanes. At the plasma level, activation of the complement (C3a, C5a, and their desarginated products) and coagulation pathways interacts with the process as products generated in the fluid phase may in turn trigger and sustain cell activation. Other agents play a role in the pathophysiology of sepsis such as surface-expressed and soluble adhesion molecules, kinins, thrombin, myocardial depressant substance(s), endorphin, and heat shock proteins.

Ethylene oxide (ETO) is presently the most commonly used sterilization method for medical devices. Although alternative sterilization modes such as steam sterilization have been suggested, the effect of steam on dialysis-induced cytokine release is unknown. We enrolled 9 patients on chronic hemodialysis and evaluated at different intervals IL- 1βproduction while treated with ETO (NC1785–Bellco) and steam sterilized NC 1785S-Bellco) Synthetically Modified Cellulose (SMC). A basal test during treatment with NC 1785 was performed (A); the same test was set up 4 weeks after treatment with NC 1785S (B) and, lastly, 4 weeks after returning to NC 1785 (C). Peripheral blood mononuclear cells (PBMC) were purified before and after the dialysis session, were isolated on a Ficoll/Hypaque gradient and incubated for 24 h. Spontaneous IL-1β release was evaluated in the supernatant and in the lysate. In A, IL-1βlevels were (in pg/ml/106 cells, in supernatant and lysate, respectively): 5.8 ± 4.8 and 7.6 ± 5.2 in pre-HD and 4.68 ± 3.6 and 9.7 ± 6.65 in post-HD. These levels showed a clear reduction in B: 2.5 ± 2.2 and 4.4 ± 3.1 in pre-HD, and 4.35 ± 6.6 and 7.52 ± 7.22 in post-HD. In the C test, 4 weeks after the return to the ETO membrane, IL-1βlevels remained unchanged: 2.9 ± 1.8 and 4.5 ± 3.1 in pre-HD; and 2.6 ± 3 and 5.7 ± 6.6 in post-HD. Statistical analysis showed significant changes in the pre-HD levels both in supernatant (p < 0.04) and in lysate (p < 0.04). Steam sterilization of SMC induced a lower spontaneous IL-1β release, but this effect was not statistically significant due to the large inter-individual variation. Hence, contrary to claims of better biocompatibility, steam sterilization does not result in a reduced production of pro-inflammatory IL-1β.

Cardiovascular complications caused by an accelerated atherosclerotic disease represent the largest single cause of mortality in chronic renal failure patients. The rapidly developing atherosclerosis of the uremic syndrome appears to be caused by a synergism of different mechanisms, such as malnutrition, oxidative stress and genetic factors. Recent studies provide evidence that chronic inflammation plays an important role in the pathogenesis of cardiovascular diseases. Hyperphosphatemia and an increased calcium-phosphate ion product have also been associated with an increased risk of death. Cardiovascular calcifications secondary to increases in phosphate and calcium load in dialysis patients might exert an important contribution to the excess cardiovascular mortality and morbidity in dialysis patients. Elevated serum levels of plasma C-reactive protein (CRP) are associated with the extent and severity of the atherosclerotic processes as well as with an increased risk of experiencing myocardial infarction and sudden cardiac death in apparently healthy subjects. In patients affected by pre-dialytic renal failure increased levels of CRP and IL-6 were recorded in 25% of our population; CRP and IL-6 were inversely related with renal function. These data suggest the activation - even in the predialytic phase of renal failure - of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome. In recent years we have investigated the hypothesis that the chronic inflammatory state of the uremic patient could be at least in part due to the dialytic technique. We have shown that the increase of CRP in stable dialysis patients may be due to the stimulation of monocyte/macrophage by backfiltration of dialysate contaminants. During conventional dialysis, a positive calcium balance and a concomitant inflammatory state may act as cofactors in the development of cardiovascular calcifications. We suggest that this hypothesis should be verified by clinical studies. A reevaluation of the ideal calcium levels in the dialysate is warranted: a neutral intradialytic calcium balance is probably more appropriate, although not easily attainable.

Hemodialysis monitors represent a frequent site for bacterial contamination.Two different disinfection protocols on a new device (Formula(R), Bellco) have been compared: only chemical or chemical plus heat disinfection by means of CFU, and LAL test. The endotoxin removing capacity of ultrafilter was tested with varying lipopolysaccharide concentrations.Similar results were obtained with heat disinfection compared to chemical disinfection (CFU and LAL test). The LAL test (chromogenic and gel-clot) showed that the ultrafilter performance decreased with use and was significant after 200 operating hours.Heat disinfection between dialysis shifts and chemical disinfection at the end of the day exclude bacterial contamination of the monitor as well as chemical disinfection; LAL test is a useful and simple tool to assess the ultrafilters performance in each Center.

Blood pressure control is important during dialysis and the interdialytic period because of the frequency and potential seriousness of hypotension and hypertension. Water and sodium removal play an important role in the genesis of intradialytic cardiovascular instability or hypertension. Changing dialysate sodium concentrations without the aid of a kinetic model can sometimes give good results but is only an empirical approach. Therefore, this clinical trial was designed to prospectively investigate the advantages of changes in the sodium pool on the blood pressure profile of patients undergoing paired filtration dialysis (PFD). The hypothesis to be tested is whether using a dialysate conductivity which, according to the conductivity kinetic model, ensures that the conductivity of the ultrafiltrate at the end of each dialysis session is 0.3 mS/cm more (B) or less (C) than the mean during the run-in period, improves blood pressure control either in patients prone to intradialytic hypotension or patients who are hypertensive or normotensive with antihypertensive treatment. Patients will be randomly allocated to one of two treatment sequences (where treatment A is standard PFD): AABB or ABAA for patients with intradialytic hypotension; AACC or ACAA for hypertensive patients. During the experimental phase arterial blood pressure will be measured and symptoms reported by the patients will be recorded.

This study focuses on the mechanisms responsible for monocyte activation and enhanced cytokine production in hemodialysis. Particular emphasis is given to recent recognition of a link between cytokine production and chronic inflammation following long-term complications in today's hemodialysis population, namely cardiovascular disease and malnutrition.

In hemodialysis patients, C-reactive protein (CRP), an acute-phase reactant, is a sensitive and independent marker of malnutrition, anemia, and amyloidosis. The aim of the present studies was to evaluate CRP and interleukin 6 levels in plasma samples from long-term hemodialysis patients on different extracorporeal modalities associated with or without backfiltration. Two hundred and forty-seven patients were recruited in eight hospital-based centers. All patients had been on their dialytic modality for at least 6 months. At enrollment, 46 hemodialysis patients out of 247 (18.6%) had clinical evidence of pathologies known to be associated with high CRP values. The 201 remaining patients were defined as clinically stable and were on conventional hemodialysis (34%), hemodiafiltration with infusion volumes10 liters/session (10%), hemodiafiltration with infusion volumes20 liters/session (32%), and double-chamber hemodiafiltration with infusion volumes10 liters/session (22%). Analysis of CRP values in the clinically stable patients showed that an unexpectedly high proportion (47%) of the patients had CRP values higher than 5 mg/l (taken as the upper limit in normal human subjects). The values of CRP and interleukin 6 were significantly higher in hemodiafiltration with infusion volumes10 liters/session than in hemodiafiltration with infusion volumes20 liters/session, in hemodialysis and in double-chamber hemodiafiltration. The same pattern occurred after 6 months of follow-up in 171 out of 201 clinically stable patients. Hemodialytic conditions that expose to the risk of backfiltration such as low exchange volume hemodiafiltration may induce a chronic inflammatory state as reflected by increased plasma values of both CRP and interleukin 6, thus suggesting the need for hemodialytic strategies that reduce (hemodialysis with low-permeability membranes or hemodiafiltration with infusion volumes20 liters) or eliminate (double-chamber hemodiafiltration) backfiltration of bacteria-derived contaminants.