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Biomedical subjects

Monica Bonello

Publications and source records attributed to Monica Bonello.

At least 19 recordsLinked to original sources
PubMed2007

Disinfection of dialysis monitors.

In recent years the concept of biocompatibility is not limited to the dialytic membranes, but has been substituted by a more general viewpoint where all the parameters of the dialytic treatment are taken into consideration: the interaction of blood-surfaces (the dialyzer in all its components and the hematic lines), the sterilization of all materials, the quality of the solutions utilized for dialysis and reinfusion. Numerous studies have shown that the inflammatory response in dialysis is the cause of many of the side effects of dialytic treatment itself both acute and chronic. Hypoxemia, 'first use' syndrome, hypotension, allergic-anaphylactic reactions (short-term side effects); microinflammation, malnutrition, accelerated arteriosclerosis, anemia, beta2 microglobulin amyloidosis, immunodeficiency, bone mass loss (long-term side effects), have all been reported. In this review, we will focus on the fluids utilized for hemodialysis (HD) and hemodiafiltration (HDF); we will describe the process of disinfection of the machines which produce the dialytic solutions.

Disinfectants↗
PubMed2006

Flow distribution analysis by helical scanning in polysulfone hemodialyzers: effects of fiber structure and design on flow patterns and solute clearances.

The efficiency of a hemodialyzer is largely dependent on its ability to facilitate diffusion, as this is the main mechanism by which small solutes are removed. The diffusion process can be impaired if there is a mismatch between blood and dialysate flow distribution in the dialyzer. The objective of the paper was to study the impact of different fiber bundle configurations on blood and dialysate flow distribution and urea clearances. The Optiflux 200 NR hemodialyzer was studied and the standard F 80 A hemodialyzer was used as a control for the study. Six dialyzers of each type were studied in vitro in the radiology department utilizing a new generation of helical computed tomography (CT) scan following contrast medium injection into the blood and dialysate compartment. Dynamic sequential imaging of longitudinal sections of the dialyzer was undertaken to detect flow distribution, average and peak velocities, and calculate wall shear rates. Six patients were dialyzed with 2 different dialyzers in random consecutive sequence. In these patients, 2 consecutive dialyses were carried out with identical operational parameters (Qb = 300 mL/min, Qd = 500 mL/min). In each session, blood and dialysate side urea clearances were measured at 30 and 150 min of treatment. Macroscopic and densitometrical analysis revealed that flow distribution was most homogeneous in the dialyzer with a new bundle configuration. Significantly increased urea clearances (p < 0.001) were seen with the Optiflux dialyzer compared with the standard dialyzer. In conclusion, more homogeneous dialysate blood and dialysate flow distribution and improved small solute clearances can be achieved by modifying the configuration of the filter bundle. These effects are achieved probably as a result of reduced blood to dialysate mismatch with reduction of flow channeling. The used radiological technique allows detailed flow distribution analysis and has the potential for testing future modifications to dialyzer design.

Blood Flow Velocity↗
PubMed2006

Oxidant and carbonyl stress-related apoptosis in end-stage kidney disease: impact of membrane flux.

Apoptosis is a highly regulated process which mostly affects cell-mediated immunity. In this open-label, randomized, prospective clinical study, we determined the impact in 10 hemodialysis patients treated with high-, medium-, and low-flux membranes on spontaneous or plasma-induced apoptosis, on monocytes, as well as on oxidant and carbonyl stress. High- and medium-flux membranes significantly reduced patients' plasma-dependent proapoptotic activity on U937 monocytic cell lines. Patients who had the highest levels of plasma-induced proapoptotic activity exhibited the highest plasma levels of advanced oxidation protein products (AOPPs) and carbonyls. Plasma carbonyl residues but not AOPPs were significantly lowered. Finally, a significant correlation could be drawn between the extent of plasma-induced proapoptotic activity and both plasma carbonyl and AOPP levels.

Adult↗
PubMed2005

Practice patterns in the management of acute renal failure in the critically ill patient: an international survey.

BACKGROUND: Several controversies have developed over acute renal failure (ARF) definition and treatment: which approach to patient care is most desirable and which form of renal replacement therapy (RRT) should be applied is an everyday matter of debate. There is also disagreement on clinical practice for RRT including the best timing to start, vascular access, anti-coagulation, membranes, equipment and finally, if continuous or intermittent techniques should be preferred. In this lack of harmony, the epidemiology of ARF has recently displayed an outbreak of cases in the intensive care units and nephrologists and intensivists are now called to work together in the case of such a syndrome. SUBJECTS AND METHODS: We report on the responses of 560 contributors, mostly coming from Europe, to a questionnaire submitted during the third International Course on Critical Care Nephrology held in Vicenza, Italy in June 2004. The questionnaire was divided into several sections concerning demographic and medical information, definition of ARF, practice of RRT, current opinions about clinical advantages and problems related to different RRTs and modalities, and beliefs on alternative indications to extracorporeal treatments. RESULTS: More then 200 different definitions of ARF and about 90 RRT start criteria were reported. Oliguria and RIFLE (an acronym classifying ARF in different levels of severity: Risk of renal dysfunction; Injury to the kidney; Failure of kidney function; Loss of kidney function; End-stage kidney disease.) were the most frequent criteria used to define ARF. In 10% of centres all forms of renal replacement techniques are available, and in 70% of cases two or more different techniques are available: absolute analysis of different techniques showed that continuous renal replacement therapies are utilized by 511 specialists (91%), intermittent haemodialysis by 387 (69%) and sustained low efficiency dialysis by 136 (24%). Treatment prescription showed significant differences among specialists, 60% of intensivists being uncertain on RRT dose prescription compared to 40% of nephrologists (P = 0.002). The most frequently selected dosage was '35 ml/kg/h' for urea (25%) and creatinine targets (26%), and '2-3 l/h' for the septic dose (25%). Of the participants, 90% said that they used RRT for non-renal indications, 60% although responders admitted the lack of scientific evidence as a limiting factor to its use. CONCLUSIONS: New classifications such as RIFLE criteria might improve well-known uncertainty about ARF definition. Different RRT techniques are available in most centres, but a general lack of treatment dose standardization is noted by our survey. Non-renal indications to RRT still need to find a definitive role in routine practice.

Acute Kidney Injury↗
PubMed2005

In vivo validation of the adequacy calculator for continuous renal replacement therapies.

INTRODUCTION: The study was conducted to validate in vivo the Adequacy Calculator, a Microsoft Excel-based program, designed to assess the prescription and delivery of renal replacement therapy in the critical care setting. METHODS: The design was a prospective cohort study, set in two intensive care units of teaching hospitals. The participants were 30 consecutive critically ill patients with acute renal failure treated with 106 continuous renal replacement therapies (CRRT). Urea clearance computation was performed with the Adequacy Calculator (KCALC). Simultaneous blood and effluent urea samples were collected to measure the effectively delivered urea clearance (KDEL) at the beginning of each treatment and, during 73 treatments, between the 18th and 24th treatment hour. The correlation between 179 computed and 179 measured clearances was assessed. Fractional clearances for urea were calculated as spKt/V (where sp represents single pool, K is clearance, t is time, and V is urea volume of distribution) obtained from software prescription and compared with the delivered spKt/V obtained from empirical data. RESULTS: We found that the value of clearance predicted by the calculator was strongly correlated with the value obtained from computation on blood and dialysate determination (r = 0.97) during the first 24 treatment hours, regardless of the renal replacement modality used. The delivered spKt/V (1.25) was less than prescribed (1.4) from the Adequacy Calculator by 10.7%, owing to therapy downtime. CONCLUSION: The Adequacy Calculator is a simple tool for prescribing CRRT and for predicting the delivered dose. The calculator might be a helpful tool for standardizing therapy and for comparing disparate treatments, making it possible to perform large multi-centre studies on CRRT.

Acute Kidney Injury↗
PubMed2005

Effect of daily hemodialysis on monocytes apoptosis.

Uremia is associated with a state of immune dysfunction with increased susceptibility to infection and malignancy possibly related to dysregulation of immune system cell apoptosis. Peritoneal dialysis can restore plasma apoptosis activity on monocytes compared to intermittent hemodialysis. Whether the continuous modality or diverse clearance mechanisms involved are responsible is unknown. Apoptosis rates correlate with phagocytic function highlighting the benefit of efficient toxin clearance. The plasma of 16 patients on daily hemodialysis (D-HD) was incubated with U937 monocytes and compared to 18 hemodialysis (HD) patients, 5 chronic renal failure (CRF) subjects and 5 healthy volunteers (controls). Apoptosis was evaluated by immunofluorescence microscopy dyes (Hoechst 33342, propidium iodide) and annexin V cytoflowmetry at 96 h. Plasma-induced U937 apoptosis (mean values) was significantly enhanced in D-HD (18.8 +/- 4.1), HD (19.67 +/- 5.5) and CRF patients (20.8 +/- 4.7) compared to controls (9.6 +/- 3.6; p < 0.05 for CRF vs. controls, HD vs. controls and D-HD vs. controls). No significant differences were observed between D-HD, HD and CRF sera on apoptosis rate, caspase-3 activity and phagocytic capacity of U937 monocytes. This study demonstrates that the plasma of various HD schedules was unable to reduce monocyte apoptosis induced by uremia.

Adult↗
PubMed2005

Phosphate kinetics during different dialysis modalities.

BACKGROUND: An abnormal serum phosphate concentration is common in acute renal failure patients, with a reported incidence of 65-80%. Phosphate removal and kinetics during intermittent hemodialysis (IHD) have been investigated, but there is no information on its kinetics during slow low-efficiency dialysis (SLED) and continuous renal replacement therapy (CRRT). METHODS: Eight IHD, 8 SLED, and 10 continuous venovenous hemofiltration (CVVH) patients with a residual renal clearance of <4.0 ml/min were studied during a single treatment to evaluate phosphate removal and kinetics. CVVH was studied the first 24 h after initiation. Dialysis/replacement fluid contained no phosphate. Kt/V, clearance of urea (Ku), inorganic phosphate (Kp) and solute removal was determined by direct dialysate quantification (DDQ). RESULTS: Kp recorded with the three techniques were: IHD, 126.9 +/- 18.4 ml/min; SLED, 58.0 +/- 15.8 ml/min, and CVVH, 31.5 +/- 6.0 ml/min. However, in shorter dialysis treatment the total removal of phosphate was significantly lower than in longer dialysis (IHD, 29.9 +/- 7.7 mmol; SLED, 37.6 +/- 9.6 mmol; CVVH, 66.7 +/- 18.9 mmol, p = 0.001). The duration of treatment is the only factor determining phosphate removal (r = 0.7, p < 0.0001 by linear correlation model). Like IHD, phosphate kinetics during SLED could not be explained by the two-pool kinetic model, and the rebound of phosphate extended beyond 1 h after dialysis. Rebound, however, is less marked than in short dialysis. CONCLUSION: These results are reliable evidence about amount of phosphate removal and behavior of intradialytic phosphate kinetics in renal failure patients undergoing different dialysis modalities. These data will help clinicians plan phosphate supplementation and treatment intensity.

Aged↗
PubMed2005

Rasburicase therapy in acute hyperuricemia and renal dysfunction.

Neoplastic disorders may be complicated by acute renal failure (ARF). Different tumors may cause ARF: solid tumors involving the kidney, solid tumors not of hematological origin and not primarily involving the kidney or, more frequently, rapidly developing hematological tumors. The pathogenesis of ARF is different depending on the type of cancer, but the most frequent clinical feature is the acute tumor lysis syndrome, characterized by hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia and acute, frequently oliguric, ARF. The presence of a neoplastic disorder and associated acute illness may sometimes lead to the presence of immunodysfunction, septic complications and multiple organ dysfunction. In these settings patients develop systemic inflammation and diffuse endothelial damage, related to different mediators. Among these substances, in cancer patients, high circulating levels of uric acid are a common finding. Hyperuricemia is caused by the increase of purine metabolism, which is result of the increased cellular turnover or the aggressive cancer chemotherapy regimens that worsen cell lysis and release of purine metabolites. Even if hyperuricemia is not the first insult to the kidney, its development might represent a concomitant factor aggravating other previous or simultaneous insults. The most efficient therapy for lowering uric acid is rasburicase, a recombinant form of urate oxidase, a nonhuman proteolytic enzyme that oxidizes uric acid to allantoin. It is efficacious in reducing serum uric acid levels with associated diuresis more effectively and much faster than allopurinol, and to correct renal dysfunction more rapidly than allopurinol.

Acute Disease↗
PubMed2005

A new machine for continuous renal replacement therapy: from development to clinical testing.

A new continuous renal replacement therapy machine has been designed to fulfill the expectations of nephrologists and intensivists operating in the common ground of critical care nephrology. The new equipment is called Prismaflex and it is the natural evolution of the PRISMA machine that has been utilized worldwide for continuous renal replacement therapy in the last 10 years. The authors performed a preliminary alpha-trial to establish the usability, flexibility and reliability of the new device. Accuracy was also tested by recording various operational parameters during different intermittent and continuous renal replacement modalities during 62 treatments. This article will describe our first experience with this new device and touch upon the historic and technologic background leading to its development.

Clinical Trials as Topic↗
PubMed2005

Protective effect of urate oxidase on uric acid induced-monocyte apoptosis.

Uremic patients have a higher risk of infection and malignancy than normal subjects. Previous studies have deomonstrated that monocytes isolated from uremic patients display an increased apoptosis rate compared to normal subjects; furthermore uremic plasma can increase apoptosis rates on U937, a human monocytic cell line. In several pathological conditions, precipitation of uric acid crystals can lead to renal insufficiency or acute renal failure by different mechanisms. In recent studies uric acid has been shown to induce inflammatory response from monocytes and it has been suggested to be involved in cell dysfunction. Rasburicase is a new recombinant urate oxidase developed to prevent and treat hyperuricaemia in patients with cancer or renal failure; it degrades uric acid to allantoin, a less toxic and more soluble product. In the present study, we aimed at determining whether uric acid may be a factor affecting U937 apoptosis, and whether urate oxidase may reduces or even prevent uric acid induced cell apoptosis. Hoechst staining and internucleosome ledder fragmentation of DNA showed that uric acid increased the percentage of apoptotic cells comparing to the control and that when the U937 cells were incubated with uric acid and urate oxidase the percentage of apoptosis significantly decreased (from 43+/-7% to 19+/- 3%, p<0.05). Also, the activity of caspase-8 and caspase-3 showed the same trend (caspase 3: from 2.7+/-0.53 to 1.6+/-0.42; caspase-8: from 2.2+/-0.43 to 1.3+/-0.57). A reduction of intracellular reduced glutathione (GSH) concentration was found in uric acid treated cells while the addition of urate oxidase in the uric acid incubated cells decreased the GSH extrusion. The concentration of TNF-alpha was increased in the sample incubated with uric acid comparing to the control. Uric acid is an inducer of apoptosis on U937 cell line, and therefore it may be a component of the mosaic of uremic toxins both in acute and chronic renal disease. We can hypothesize that uric acid might be directly involved in the apoptotic process trough the activation of both death receptor and mitochondrial-mediated pathways. We have, also, demonstrated that urate oxidase is able to prevent at least in part, the effect of uric acid on U937 apoptosis. This effect might be a result of different mechanisms of action.

Apoptosis↗
PubMed2004

Renal replacement therapy in acute renal failure.

Acute renal failure (ARF) is a common condition in hospitalized patients. The aetiology and physiological characteristics differ from those of chronic renal failure (CRF) and both conditions should be approached differently. At present, the approach to the management of ARF is very heterogeneous. Attempts have therefore been made to improve consensus and to standardize treatment in the Acute Dialysis Quality Initiative (ADQI). Technology for the treatment of ARF is expanding. Traditional intermittent haemodialysis (IHD) is still a major treatment modality but continuous renal replacement therapies (CRRT) and slow, low-efficiency daily dialysis (SLEDD) are commonly used alternatives. Each modality has advantages and disadvantages, but to date no evidence exists for the superiority of one over the other. On the other hand, the availability of multiple options allows us to provide tailor-made treatment: the best modality is chosen depending on local expertise and the individual clinical scenario. Practice guidelines based on the best available evidence and the author's opinion are suggested.

Acute Kidney Injury↗
PubMed2004

Monocyte apoptosis in uremia is normalized with continuous blood purification modalities.

Uremia is associated with a state of immune dysfunction. Dysregulation of homeostasis may be directly related to abnormal apoptosis regulation in uremia, which is crucial for the maintenance of the biological system. We demonstrated that plasma from three groups of uremic subjects, i.e. hemodialysis (HD) patients, peritoneal dialysis (PD) patients and patients with predialysis chronic renal failure (CRF), has different apoptotic potential on U937 monocytes. The plasma of HD and CRF subjects when incubated with U937 cells induced higher levels of apoptosis compared with that of PD and control subjects (HD 26.08 +/- 11.39, CRF 24.87 +/- 9.07, PD 12.13 +/- 4.51, controls 11.69 +/- 4.02). Furthermore, the phagocytic ability of U937 cells incubated with the various plasma demonstrated an impaired response in the HD and CRF subjects (HD 27.56 +/- 6.67, CRF 30.24 +/- 9.08, PD 36.55 +/- 9.80, controls 40.04 +/- 6.98). These results suggest that continuous blood purification, such as in PD, may have advantages over intermittent therapies in removing uremic apoptotic molecules and potentially maintaining biological function and homeostasis.

Apoptosis↗
PubMed2004

Extracorporeal therapies in non-renal disease: treatment of sepsis and the peak concentration hypothesis.

In the setting of intensive care, patients with acute renal failure often present a clinical picture of the systemic inflammatory response syndrome (SIRS). SIRS can be caused by bacterial stimuli or by non-microbiological stimuli that induce a significant inflammatory response. When this response is exaggerated, the patient experiences multiple organ system failure and a condition of sepsis also defined as a systemic malignant inflammation. This is mostly characterized by an invasion of cytokines and other pro-inflammatory mediators into the systemic circulation where major biological effects take place, including vasopermeabilization, hypotension and shock. At the same time, the monocyte of the septic patient seems to be hyporesponsive to inflammatory stimuli to a certain extent. In this condition, the patient faces a situation of hyperinflammation but at the same time of immunodepression expressing a clinical entity defined as counter anti-inflammatory response syndrome. The general picture of the clinical disorder is therefore better characterized by an immunodysregulation than by a simple pro- or anti-inflammatory disorder. Due to the short half-life of cytokines and other mediators spilled over into the circulation, it is extremely difficult to approach the problem at the right moment with the right pharmacological agent. For these reasons, the peak concentration hypothesis suggests that continuous renal replacement therapies, due to their continuity and unspecific capacity of removal, might be beneficial in cutting the peaks of the concentrations of both pro- and anti-inflammatory mediators, restoring a situation of immunohomeostasis. Thus the patient may benefit from a lesser degree of immunodysregulation and he/she may restore a close-to-normal capacity of response to exogenous stimuli.

Animals↗
PubMed2003

Interpreting the mechanisms of continuous renal replacement therapy in sepsis: the peak concentration hypothesis.

Severe sepsis and septic shock are the primary causes of multiple organ dysfunction syndrome (MODS), which is the most frequent cause of death in intensive care unit patients. Many water-soluble mediators with pro- and anti-inflammatory action such as TNF, IL-6, IL-8, and IL-10 play a strategic role in septic syndrome. In intensive care medicine, blocking any one mediator has not led to a measurable outcome improvement in patients with sepsis. CRRT is a continuously acting therapy, which removes in a nonselective way pro- and anti-inflammatory mediators; "the peak concentration hypothesis" is the concept of cutting peaks of soluble mediators through continuous hemofiltration. Furthermore, there is evidence of increased efficacy of high-volume hemofiltration compared to conventional CVVH, and other blood purification techniques that utilize large-pore membranes or sorbent plasmafiltration are conceptually interesting.

Acute Kidney Injury↗