The role of middle molecules in uremia--preliminary report of an international survey of nephrologists and scientists.
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Biomedical subjects
Publications and source records attributed to C Ronco.
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The analysis of flow distribution in cartridges designed for hemoperfusion is extremely important. Taking advantage of a new imaging technique, based on the analysis of a helical scanner-generated imaging sequence, we studied the blood flow distribution in a series of cartridges for extracorporeal removal of endotoxin. Cartridges with improved design were compared to cartridges with a standard design. The improved design consists in a different structure of the holes of the distributor of the flow within the adsorbent unit. Cartridges were studied in vitro with human blood from voluntary donors at blood flows of 100 and 250 ml/min. The progression of density in specific regions of interest (ROI) was analyzed to detect the distribution of the dye injected in the blood circuit. The study demonstrates that both at 100 ml/min and at 250 ml/min of blood flow, the progression of flow appears more homogeneous in the devices with improved design. In detail, the flow distribution measured by the incremental density values detected in the ROIs of the proximal comers (close to the arterial port) and in the ROIs of the central region of the device (close to the inner wall of the case) displays a significant difference between the standard and the improved device. The ROIs studied in the standard devices display a slower increase in density and significantly lower absolute values expressed in Hounsfield units. The experimental method utilized to analyze flow distribution seems to represent an important means to study the performance and design of this type of device.
BACKGROUND: Achieving "adequacy of dialysis" includes the maintenance of normal serum phosphate concentrations and is an important therapeutic goal in the treatment of acute renal failure (ARF). It is unknown whether this goal is best achieved with intermittent or continuous renal replacement therapy. METHODS: We compared the effects of continuous veno-venous hemodiafiltration (CVVHDF) and intermittent hemodialysis (IHD) on serum phosphate concentrations using daily morning blood tests in 88 consecutive intensive care patients half of which were treated with IHD and half with CRRT RESULTS: Mean patient age was 54+/-14 years for IHD and 60+/-14 years for CVVHDF (NS). However, patients who received CVVHDF were more critically ill (mean APACHE II scores: 24.4+/-5.1 for IHD vs. 29.2+/-5.7 for CVVHDF, p<0.003). Before treatment, the serum phosphate concentration was 2.04+/-0.16 mmoll L for IHD and 1.96+/-0.17 mmoll L for CVVHDF (NS), with abnormal values in 79.4% of IHD patients and in 64.8% of CVVHDF patients (NS). During treatment, CVVHDF induced a greater reduction in serum phosphate (p=0.02) during the first 48 hours and conferred superior subsequent control of hyperphosphatemia (achieved in 64.6% of observations during CVVHDF vs. 41.8% during IHD; p<0.0001). The serum phosphate concentration was also more likely to be within the normal range during CVVHDF (55.3% vs.36.2%; p<0.0001). There was a trend toward more frequent hypophosphatemia (9.3% vs. 5.6%; P<0.1) during CVVHDF CONCLUSIONS: Abnormal serum phosphate concentrations are frequent in ARF patients before and during renal replacement, however, normalization of phosphatemia is achieved more frequently with CVVHDF.
INTRODUCTION: Physical properties of filters for continous renal replacement therapy have a great impact on biocompatibility. According to Poiseuille's law, a filter with more and shorter hollow fibers should offer a decreased pressure drop and, therefore, lower transmembrane pressure (TMP). The aim of this study was to study the effect of a new filter configuration in terms of TMP and clotting compared with the standard configuration. METHODS: In a prospective randomized cross-over study 2 polysulphone hollow fiber hemofilters, one handmade, which differed only in length and number of hollow fibers were compared. In each group 12 filters were investigated during continous venovenous hemofiltration in patients with acute renal failure due to septic shock. Pressures were measured every 3 hours and running time until filter clotting was documented. Mediators before and after the filter, at the end of treatment and in filtrate were assessed. RESULTS: The standard filter with longer hollow fibers had significantly lower TMPs (106 vs. 194 mmHg, p=0.02) and longer running times (1276 vs. 851 min, p=0.04). There were no differences in hematocrit, total protein, cellular and plasmatic coagulation or blood temperature. No significant elimination of mediators was shown. CONCLUSION: In contrast to our expectations, the filter with the longer hollow fibers had a better performance, as it ran longer and had lower TMP This may be due to slower blood flow leading to an increase in blood viscosity in a filter with a larger cross section.
Modern dialysis membranes need to fulfil two basic requirements. Firstly, the membrane structure, defined in terms of the size, structure and distribution of the pores at the inner separating layer of the membrane must be such that uraemic solutes of a defined molecular-weight range are selectively removed. Secondly, the physical and chemical properties of the blood-contacting surface must be such that minimal blood-material interactions take place that could either affect the functioning of the membrane, or, cause adverse reactions for the patient. A new polysulfone dialysis membrane, Helixone, has been developed specifically for the elimination of larger uraemic toxins using convective therapy modalities such as haemodiafiltration. The membrane is characterised by the nanoscale modulation of the innermost surface structures that lead to significantly increased sieving coefficients for molecules such as beta2-microglobulin, while maintaining the extremely low albumin removal property of the high-flux Fresenius Polysulfone membrane. A recent publication (Ronco C, Bowry SK. Nanoscale modulation of the pore dimensions, size distribution and structure of a new polysulfone-based high-flux dialysis membrane. Int J Artif Organs 2001; 24: 726-35) described the characterisation of the membrane of Helixone in terms of the membrane wall structure- and permeation-related parameters. In this paper, we describe the analysis of membrane surface parameters that influence the biocompatibility as well as the functioning of a membrane. The degree of roughness and the type of chemical groups of a blood-contacting surface are two of the main determinants of the biocompatibility characteristics of a membrane. The surface elemental composition of Helixone was determined using electron spectroscopy for elemental analysis (ESCA) while the surface topography of the membrane was evaluated using atomic force microscopy (AFM). The analysis showed that Helixone has an improved, smoother blood-contacting surface and retains the essential surface chemistry, and therefore the acknowledged biocompatibility profile, of the Fresenius Polysulfone membrane.
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 (beta2-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 gamma-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.
Current haemodialysis therapy modalities such as haemodiafiltration enhance the removal of larger uraemic solutes from the blood of patients on end-stage renal disease. A number of clinical investigations have demonstrated the clinical benefits of such therapies in contributing towards better patient survival rates and an improved quality of life. A fundamental prerequisite to the application of convective treatment modalities is the availability of appropriate, technologically-advanced high-flux dialysis membranes that are able to eliminate larger uraemic substances with high efficiency but without causing an excessive leakage of useful proteins. A new membrane, Helixone, has been developed specifically to meet the present-day requirements of high-flux dialysis and haemodiafiltration therapies involving large substitution rates. The application of nanotechnology fabrication principles and procedures has enabled the development of a membrane having highly-defined inner, separating layer surface structures that offer minimal resistance to the removal of large molecular weight substances across the membrane; for the first time, pore size dimensions, pore size distribution and pore geometry have been modulated and controlled at the nanoscale level for Helixone. This paper describes the characterisation of the essential structure- and permeation-related parameters of the new membrane using a number of physical analytical techniques.
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Continuous renal replacement therapy (CRRT) was first described in 1977 for the treatment of diuretic-unresponsive fluid overload in the intensive care unit (ICU). Since that time this treatment has undergone a remarkable technical and conceptual evolution. It is now available in most tertiary ICUs around the world and has almost completely replaced intermittent haemodialysis (IHD) in some countries. Specially made machines are now available, and venovenous therapies that use blood pumps have replaced simpler techniques. Although, it remains controversial whether CRRT decreases mortality when compared with IHD, much evidence suggests that it is physiologically superior. The use of CRRT has also spurred renewed interest in the broader concept of blood purification, particularly in septic states. Experimental evidence suggests that this is a promising approach to the management of septic shock in critically ill patients. The evolution and use of CRRT is likely to continue and grow over the next decade.
BACKGROUND: Continuous veno-venous haemofiltration is increasingly used to treat acute renal failure in critically ill patients, but a clear definition of an adequate treatment dose has not been established. We undertook a prospective randomised study of the impact different ultrafiltration doses in continuous renal replacement therapy on survival. METHODS: We enrolled 425 patients, with a mean age of 61 years, in intensive care who had acute renal failure. Patients were randomly assigned ultrafiltration at 20 mL h(-1) kg(-1) (group 1, n=146), 35 mL h(-1) kg(-1) (group 2, n=139), or 45 mL h(-1) kg(-1) (group 3, n=140). The primary endpoint was survival at 15 days after stopping haemofiltration. We also assessed recovery of renal function and frequency of complications during treatment. Analysis was by intention to treat. RESULTS: Survival in group 1 was significantly lower than in groups 2 (p=0.0007) and 3 (p=0.0013). Survival in groups 2 and 3 did not differ significantly (p=0.87). Adjustment for possible confounding factors did not change the pattern of differences among the groups. Survivors in all groups had lower concentrations of blood urea nitrogen before continuous haemofiltration was started than non-survivors. 95%, 92%, and 90% of survivors in groups 1, 2, and 3, respectively, had full recovery of renal function. The frequency of complications was similarly low in all groups. INTERPRETATION: Mortality among these critically ill patients was high, but increase in the rate of ultrafiltration improved survival significantly. We recommend that ultrafiltration should be prescribed according to patient's bodyweight and should reach at least 35 mL h(-1) kg(-1).
OBJECTIVE: To examine the ethical approach of intensivists and nephrologists to continuous renal replacement therapy (CRRT). DESIGN: A questionnaire. SETTING: The First International Course on Critical Care Nephrology. PARTICIPANTS: The participants in the course (around 500). RESULTS: Most participants think that establishing ethical criteria for managing CRRT is a medical task, as clinicians have adequate criteria for defining futility. However, many responders would grant the request of starting futile CRRT or would maintain it if requested by the family. Only 55% believe that informed consent is necessary for initiating CRRT; one out of four would start or maintain unwanted life-saving CRRT. In case of lack of equipment, the majority would select the patients, excluding the worst one or on a "first-come, first-served" basis. Withholding and withdrawing are regarded differently by most responders. Again, most think that every vital support should be withdrawn when futile, but practical and psychological aspects still influence the final decision. Responders think that ethics critical care committees can help in the management of ethical problems in ICU. CONCLUSIONS: Our results show that several ethical questions are still unsolved and that practical and psychological aspects of the treatment process can be stronger than bioethical principles.