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Biomedical subjects

Claudio Ronco

Publications and source records attributed to Claudio Ronco.

At least 73 records · Page 4Linked to original sources
PubMed2005

Consensus development in acute renal failure: The Acute Dialysis Quality Initiative.

PURPOSE OF REVIEW: Although acute renal failure is both common and highly lethal in the intensive care unit, our understanding of the epidemiology and pathophysiology of acute renal failure is limited, and treatment for acute renal failure is extremely variable around the world. The general lack of consensus with regard to definitions, prevention, and treatment of acute renal failure has limited progress in this field. RECENT FINDINGS: Consensus in acute renal failure requires establishing a framework in which intensivists, nephrologists, pharmacologists, and others who care for critically ill patients with or at risk for acute renal failure can reach consensus and develop evidence-based practice guidelines. The Acute Dialysis Quality Initiative seeks to provide an objective, dispassionate distillation of the literature and description of the current state of practice of dialysis and related therapies as they are applied to acutely ill patients. The purposes of Acute Dialysis Quality Initiative are first, to develop a consensus of opinion, with evidence where possible, on best practice; and second, to articulate a research agenda to focus on important unanswered questions. SUMMARY: Broad consensus in the diagnosis and management of acute renal failure and in the use of blood purification in nonrenal critical illness is achievable. Standardization of definitions, practice, and research methodology is urgently needed, and specific proposals have been made by an international, interdisciplinary group.

Acute Kidney Injury↗
PubMed2005

Continuously functioning artificial nephron system: the promise of nanotechnology.

Nearly 900,000 patients worldwide have end-stage renal disease and require dialysis or kidney transplantation. Despite the availability of these forms of renal replacement therapy for nearly four decades, mortality and morbidity are high and patients often have a poor quality of life. We have developed a human nephron filter (HNF) utilizing nanotechnology that would eventually make feasible a continuously functioning, wearable or implantable artificial kidney. The device consists of two membranes operating in series within one device cartridge. The first membrane mimics the function of the glomerulus, using convective transport to generate a plasma ultrafiltrate containing all solutes approaching the molecular weight of albumin. The second membrane mimics the function of the renal tubules, selectively reclaiming designated solutes to maintain body homeostasis. No dialysis solution is used in this device. The HNF has been computer-modeled, and operating 12 hr per day, 7 days per week the HNF provides the equivalent of 30 mL/min glomerular filtration rate (compared to half that amount for conventional thrice-weekly hemodialysis). Animal studies should begin in the next 1 to 2 years, and clinical trials would then follow 1 to 2 years subsequent. The HNF system, by eliminating dialysate and utilizing a novel membrane system created through applied nanotechnology, represents a breakthrough in renal replacement therapy based on the functioning of native kidneys. The enhanced solute removal and wearable design should substantially improve patient outcomes and quality of life.

Filtration↗
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

Absence of NF-kappaB activation by a new polystyrene-type adsorbent designed for hemoperfusion.

AIM: The aim of the study was to evaluate biocompatibility of anew polystyrene-type adsorbent (BetaSorb) designed for hemoperfusion, using second-level biomolecular analyses. The device has recently been developed to enhance beta2-microglobulin removal during hemodialysis. Molecular structure and chemical modifications of the surface beads of this cartridge should prevent exposure of dense hydrophobic surface sites to proteins, and avoid the major drawbacks of previous polystyrene-type adsorbent materials. METHODS: Whole blood of healthy donors was incubated in sterile minicolumns packed with BetaSorb Cuprophan, Hemophan, polysulfone and cellulose acetate. In parallel experiments, whole blood was recirculated for 180 min in a sham dialysis circuit equipped with the study sorbent or Hemophan or polysulfone. Biocompatibility was assessed by means of new biomolecular approaches focused on nuclear factor kappaB (NF-kappaB) activation (assessed by electrophoretic mobility shift assay), TNF-alpha and IL-1beta gene expression (evaluated by real-time PCR), TNF-alpha and IL-1beta production (measured by Western blot assay and ELISA), nitric oxide (NO) generation (detected by electron paramagnetic resonance), free oxygen radical production (by chemiluminescence in a biological assay) and the generation of the complement breakdown product C3d. RESULTS: In coincubation experiments, 5-min contact with any dialysis device, but BetaSorb, was enough to induce activation of NF-kappaB. The amount of TNF-alpha precursor form was found to increase after 5 min of exposure to each tested polymer, but no traces of mature forms of TNF-alpha or IL-1beta were detected in in vitro experimental conditions using healthy blood. NO and free oxygen radical generation were significantly lower in blood samples exposed to BetaSorb than in control dialysis devices. C3d levels were found to be increased with Hemophan, unaffected by polysulfone, and remarkably decreased with the BetaSorb device. In the sham hemodialysis experiments, NF-kappaB activation and C3d and NO profiles were similar to direct incubation experiments. Compared to basal levels, quantitation of TNF-alpha and IL-1beta mRNA revealed a 15- and 9-fold increase, respectively, in samples exposed to Hemophan for 180 min. CONCLUSIONS: The new BetaSorb device not only appears to be highly biocompatible, but shares properties that make it probably able to interfere with the activation of the inflammatory state.

Adsorption↗
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

Mechanisms of solute transport in extracorporeal therapies.

Diffusion and convection are the main mechanisms involved in the membrane separation processes occurring in extracorporeal hemodialysis. Operational parameters should be optimized in hollow fiber hemodialyzers to achieve the maximal efficiency. The nature of blood which is a non Newtonian fluid, requires specific attention in the design of dialyzers to ensure that the blood compartment operates properly. Similar attention must be placed in the design of the dialysate compartment to ensure a homogeneous distribution of the fluid and to prevent blood to dialysate flow mismatch. Finally, the membrane represents the third component of the hemodialyzer. Membrane performance depends on the used biomaterial, its biocompatibility, the thickness, the hydrophilic-hydrophobic mixture, the hydraulic permeability and the number and diameter of the pores. In this setting, diffusion and convection tend to reciprocally interfere, producing a final result that depends on the prevalence of one or the other mechanism for every specific solute.

Biological Transport↗
PubMed2005

Mathematical model to characterize internal filtration.

Convective-diffusive dialysis techniques have recently gained considerable favor. Indeed, convective fluxes through dialyzer membranes have been demonstrated to play a role in enhancing the clearance of middle-molecular-weight solutes. An interesting opportunity is given by exploiting the internal filtration (IF)/back filtration mechanism that occurs spontaneously in high-flux dialyzers, but is difficult to quantify. In view of overcoming this drawback, a semi-empirical, lumped-parameter mathematical model for characterization of IF phenomena was developed. The model considers a dialyzer as composed by N adjacent axial blocks. For each block, hydrodynamics in the blood and dialysate compartments are determined considering hydraulic resistance and calculating local filtration. Blood viscosity and oncotic pressure are calculated locally based on hematocrit and protein concentration. Resistance parameters were determined experimentally for the BS-UL (Toray Industries Inc., Tokyo, Japan) dialyzers. The set of equations describing the model, implemented into a software program, is solved using a numerical method. Simulations allow highlighting the role of device-, treatment- and patient-dependent parameters in affecting IF. Provided an extensive validation is carried out, the use of a mathematical model could be the key to make IF more understandable and its use reliable in clinical practice.

Computer Simulation↗
PubMed2005

Use of segmental multifrequency bioimpedance spectroscopy in hemodialysis.

Whole body bioimpedance (BI) appears to be accurate and reproducible in the assessment of body composition, but does not appear useful for estimation of dry weight. Segmental BI has been used for the assessment of muscle mass in body segments, such as arms or legs and may be useful for rehabilitation studies. A promising new development is the application of segmental BI for dry weight determination. Changes in extracellular volume of the calf are recorded continuously during HD, thereby allowing the detection of a time-point at which no further volume is removed from the calf despite ongoing ultrafiltration (UF). Continuation of UF beyond this point is associated with an increased risk of intradialytic hypotension. This new technology may help optimizing the prescription of dry weight and UF rates in hemodialysis patients.

Body Composition↗
PubMed2005

The cardiovascular burden of the dialysis patient: the impact of dialysis technology.

There is widespread recognition that the poor survival rates of dialysis patients, attributed predominantly to cardiovascular disease, need to be addressed and improved. In this paper, we relate diverse aspects of modern dialysis technology with factors that are considered to contribute towards increased mortality and morbidity in the dialysis population. Firstly, we assess the overall cardiovascular burden of the dialysis patient: it is the sum of uraemia-related risk factors (URRF), traditional risk factors and dialysis-therapy-related factors. Secondly, we describe how key components of the dialysis procedure may be directly related to the more common URRF: the dialyser and the membrane, microbiological quality of water and dialysate, treatment modality and online monitory equipment. The judicious selection and application of these components may collectively help improve patient outcomes in hemodialysis therapy.

Cardiovascular Diseases↗
PubMed2005

Biosimilars, generic versions of the first generation of therapeutic proteins: do they exist?

This contribution describes the present regulatory status in the EU of biosimilars, the generic versions of the first generation of therapeutic proteins. It points out why and where recombinant protein molecules and low-molecular-weight drugs differ in their behaviour and why biosimilars should be handled differently than generic low-molecular-weight drugs. This information is important for practitioners (pharmacists and physicians) while selecting the best supplier of a therapeutic protein.

Antibody Formation↗
PubMed2005

Slow continuous intravenous plasmapheresis (SCIP): clinical applications and hemostability of extracorporeal ultrafiltration.

An intravenous plasmapheresis catheter which excludes >99.4% of platelets from external ultrafiltration circuits is currently undergoing safety and efficacy trials for fluid removal from NYHA class II-IV congestive heart failure patients resistant to diuretic drug therapy. In animals, the SCIP catheter allowed a four fold increase in ultrafiltration efficiency without hemolysis, hemoinstability or external cartridge changes in 72 hours of treatment. Further, systemic anticoagulation was not required. These techniques might be envisioned for treatment of fluid overload in heart failure, surgery or trauma and may have applications in therapeutic apheresis, venous thrombosis, liver disease or autologous tissue engineering.

Animals↗
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

Dialysis patients and cardiovascular problems: can technology solve the complex equation?

Patients with end-stage kidney disease undergoing chronic hemodialysis present higher mortality rates compared with the general population. Once patients are on hemodialysis, the risk of cardiovascular death is approximately 30-times higher than the general population, and still remains 10- to 20-times higher after stratification for age, gender and presence of diabetes. Approximately half of patient deaths on dialysis are attributed to cardiovascular causes, including coronary heart disease, cerebrovascular disease, peripheral vascular disease and heart failure. The cardiovascular burden of the hemodialysis patient arises from three different sources: risks inherent to the patient and the uremic syndrome, traditional risk factors and risk factors related to the dialysis therapy. Based on these considerations and the fact that several aspects of the dialysis procedure can cause either a cardiovascular burden or modify the burden already present, new technologies should be directed towards the approach of a possible 'cardioprotective dialysis therapy'. This approach may significantly contribute new techniques and new dialysis machines. Born to make dialysis easy and safe, the new machines feature several options that make monitoring and online hemodiafiltration a simple routine. These and other features could make dialysis better tolerated and more efficient in protecting from fatal cardiovascular events.

Biotechnology↗
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↗