Background: The study describes the structure and operational characteristics of a new wearable s... more Background: The study describes the structure and operational characteristics of a new wearable system for continuous ambulatory peritoneal dialysis (CAPD) for chronic kidney disease patients. Methods: We designed a wearable system consisting of: (1) a double lumen peritoneal catheter; (2) a dialysate outflow line; (3) a miniaturized rotary pump; (4) a circuit for dialysate regeneration featuring a waterproof container with 4 cartridges in parallel with a mixture of activated carbon and polystyrenic resins; (5) a filter for deaeration and microbiological safety; (6) a dialysate inflow line, and (7) a handheld computer as a remote control. The system has been tested circulating 12 liters of exhausted PD solution through the experimental adsorption unit at a rate of 20 ml/min. Creatinine, β2-microglobulin (β2-MG) and angiogenin were measured before and after the adsorption unit at baseline, and after 4 and 10 h of use. Results: The cartridges containing polystyrenic resin completely r...
Diffusion and convection are the main mechanisms involved in the membrane separation processes oc... more 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...
Sepsis is the leading cause of acute renal failure (ARF) and mortality in intensive care units (I... more Sepsis is the leading cause of acute renal failure (ARF) and mortality in intensive care units (ICU)[1–3]. It generally develops as a result of the host response to infection [4]. The pathogenesis of sepsis represents a complex mosaic of interconnected events in respect ...
Dialysis forms the cornerstone of therapy for most patients with end-stage renal disease (ESRD) a... more Dialysis forms the cornerstone of therapy for most patients with end-stage renal disease (ESRD) and many patients with acute renal failure (ARF). Consequently, it is imperative that clinicians managing these patients understand the fundamental principles of dialytic therapies, especially those having a biologic basis. In this chapter, many of these principles are reviewed. The topic of uremic toxicity is first addressed, with emphasis on the classification of uremic toxins based on molecular weight. After a frame of reference is established with a discussion of toxin elimination mechanisms for the native kidney, the dialytic solute removal mechanisms (diffusion, convection, and adsorption) broadly applicable to all renal replacement therapies are reviewed. The relative importance of these mechanisms in the different therapies used in both the ESRD and ARF settings will then be discussed. As the major determinant of overall efficiency of hemodialysis (HD), the most commonly applied renal replacement therapy, diffusive solute removal will be rigorously assessed by applying a “resistance-in-series” model to a dialyser. In much the same way, fluid and mass transfer in peritoneal dialysis will be assessed by examining the elements of the system: peritoneal microcirculation, peritoneal membrane, and the dialysate compartment. Finally, from a kinetic perspective, the differences between intermittent, continuous, and semicontinuous therapies will be discussed, with emphasis on quantification of solute removal.
The risk of developing acute kidney injury (AKI) is significantly increased in the elderly. It is... more The risk of developing acute kidney injury (AKI) is significantly increased in the elderly. It is the age-related renal and systemic changes as well as frequent comorbidities that render older individuals greatly susceptible to acute renal impairment. Although most often multifactorial, specific etiologies such as renal hypoperfusion due to cardiac failure, dehydration or hypotension of any cause, as well as sepsis, drug toxicity, surgery, or obstructive causes are often present. Contrast-induced nephropathy and atheroembolic disease are also frequently seen, especially in an acute care setting. Serum creatinine is most commonly used for diagnosis, despite it having several limitations, especially in the elderly. The mainstay of management is prevention of further deterioration, as the chances of renal recovery may be lower in older patients.
The first of this pair of 'pro/con' Viewpoints sets out the case for the superiority of c... more The first of this pair of 'pro/con' Viewpoints sets out the case for the superiority of continuous renal replacement therapy over intermittent hemodialysis in critically ill patients with acute kidney injury. Forming the basis of the author's argument is the notion that by attempting to correct in a few minutes physiological derangements that have developed over hours or days, intermittent hemodialysis is aggressive and unphysiological; by contrast, continuous renal replacement therapy corrects derangements gently and slowly, like the native kidneys.
Fluid overload may occur in patients with congestive heart failure, especially when there is asso... more Fluid overload may occur in patients with congestive heart failure, especially when there is associated acute renal failure. When the pharmacological approach is not sufficient to maintain the patient's fluid balance, extracorporeal therapies must be instituted. However, since the ultrafiltration rate may be faster than fluid refilling from the interstitial space, remarkable changes in the circulating blood volume may occur. This may finally result in further worsening of peripheral perfusion due to a significant drop in cardiac output. In order to prevent a fall in the circulating blood volume, slow continuous ultrafiltration (SCUF) should be employed instead of acute intermittent ultrafiltration (UF). To further improve the tolerance to extracorporeal ultrafiltration, the session can be driven by the relative blood volume change monitored on-line with adequate sensors and devices. We utilized one of these systems (Crit-Line, Hemametrics, USA) to compare the relative changes in blood volume during UF and SCUF in 22 patients with fluid overload. Variations in blood pressure were significantly greater with UF than with SCUF even in the presence of similar levels of fluid removal. The variations in blood pressure were paralleled by variations in blood volume, which were greater with UF than with SCUF. In conclusion, extracorporeal ultrafiltration can be used to control the fluid balance in congestive heart failure, but it is advisable to prescribe low ultrafiltration rates over an extended period of time. The use of on-line blood volume monitors can be of further help in improving tolerance and the hemodynamic response.
The aim of the study was to evaluate biocompatibility of anew polystyrene-type adsorbent (BetaSor... more 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. 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. 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. 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.
Background: The study describes the structure and operational characteristics of a new wearable s... more Background: The study describes the structure and operational characteristics of a new wearable system for continuous ambulatory peritoneal dialysis (CAPD) for chronic kidney disease patients. Methods: We designed a wearable system consisting of: (1) a double lumen peritoneal catheter; (2) a dialysate outflow line; (3) a miniaturized rotary pump; (4) a circuit for dialysate regeneration featuring a waterproof container with 4 cartridges in parallel with a mixture of activated carbon and polystyrenic resins; (5) a filter for deaeration and microbiological safety; (6) a dialysate inflow line, and (7) a handheld computer as a remote control. The system has been tested circulating 12 liters of exhausted PD solution through the experimental adsorption unit at a rate of 20 ml/min. Creatinine, β2-microglobulin (β2-MG) and angiogenin were measured before and after the adsorption unit at baseline, and after 4 and 10 h of use. Results: The cartridges containing polystyrenic resin completely r...
Diffusion and convection are the main mechanisms involved in the membrane separation processes oc... more 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...
Sepsis is the leading cause of acute renal failure (ARF) and mortality in intensive care units (I... more Sepsis is the leading cause of acute renal failure (ARF) and mortality in intensive care units (ICU)[1–3]. It generally develops as a result of the host response to infection [4]. The pathogenesis of sepsis represents a complex mosaic of interconnected events in respect ...
Dialysis forms the cornerstone of therapy for most patients with end-stage renal disease (ESRD) a... more Dialysis forms the cornerstone of therapy for most patients with end-stage renal disease (ESRD) and many patients with acute renal failure (ARF). Consequently, it is imperative that clinicians managing these patients understand the fundamental principles of dialytic therapies, especially those having a biologic basis. In this chapter, many of these principles are reviewed. The topic of uremic toxicity is first addressed, with emphasis on the classification of uremic toxins based on molecular weight. After a frame of reference is established with a discussion of toxin elimination mechanisms for the native kidney, the dialytic solute removal mechanisms (diffusion, convection, and adsorption) broadly applicable to all renal replacement therapies are reviewed. The relative importance of these mechanisms in the different therapies used in both the ESRD and ARF settings will then be discussed. As the major determinant of overall efficiency of hemodialysis (HD), the most commonly applied renal replacement therapy, diffusive solute removal will be rigorously assessed by applying a “resistance-in-series” model to a dialyser. In much the same way, fluid and mass transfer in peritoneal dialysis will be assessed by examining the elements of the system: peritoneal microcirculation, peritoneal membrane, and the dialysate compartment. Finally, from a kinetic perspective, the differences between intermittent, continuous, and semicontinuous therapies will be discussed, with emphasis on quantification of solute removal.
The risk of developing acute kidney injury (AKI) is significantly increased in the elderly. It is... more The risk of developing acute kidney injury (AKI) is significantly increased in the elderly. It is the age-related renal and systemic changes as well as frequent comorbidities that render older individuals greatly susceptible to acute renal impairment. Although most often multifactorial, specific etiologies such as renal hypoperfusion due to cardiac failure, dehydration or hypotension of any cause, as well as sepsis, drug toxicity, surgery, or obstructive causes are often present. Contrast-induced nephropathy and atheroembolic disease are also frequently seen, especially in an acute care setting. Serum creatinine is most commonly used for diagnosis, despite it having several limitations, especially in the elderly. The mainstay of management is prevention of further deterioration, as the chances of renal recovery may be lower in older patients.
The first of this pair of 'pro/con' Viewpoints sets out the case for the superiority of c... more The first of this pair of 'pro/con' Viewpoints sets out the case for the superiority of continuous renal replacement therapy over intermittent hemodialysis in critically ill patients with acute kidney injury. Forming the basis of the author's argument is the notion that by attempting to correct in a few minutes physiological derangements that have developed over hours or days, intermittent hemodialysis is aggressive and unphysiological; by contrast, continuous renal replacement therapy corrects derangements gently and slowly, like the native kidneys.
Fluid overload may occur in patients with congestive heart failure, especially when there is asso... more Fluid overload may occur in patients with congestive heart failure, especially when there is associated acute renal failure. When the pharmacological approach is not sufficient to maintain the patient's fluid balance, extracorporeal therapies must be instituted. However, since the ultrafiltration rate may be faster than fluid refilling from the interstitial space, remarkable changes in the circulating blood volume may occur. This may finally result in further worsening of peripheral perfusion due to a significant drop in cardiac output. In order to prevent a fall in the circulating blood volume, slow continuous ultrafiltration (SCUF) should be employed instead of acute intermittent ultrafiltration (UF). To further improve the tolerance to extracorporeal ultrafiltration, the session can be driven by the relative blood volume change monitored on-line with adequate sensors and devices. We utilized one of these systems (Crit-Line, Hemametrics, USA) to compare the relative changes in blood volume during UF and SCUF in 22 patients with fluid overload. Variations in blood pressure were significantly greater with UF than with SCUF even in the presence of similar levels of fluid removal. The variations in blood pressure were paralleled by variations in blood volume, which were greater with UF than with SCUF. In conclusion, extracorporeal ultrafiltration can be used to control the fluid balance in congestive heart failure, but it is advisable to prescribe low ultrafiltration rates over an extended period of time. The use of on-line blood volume monitors can be of further help in improving tolerance and the hemodynamic response.
The aim of the study was to evaluate biocompatibility of anew polystyrene-type adsorbent (BetaSor... more 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. 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. 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. 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.
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Papers by Claudio Ronco