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Isolation of an immunosuppressive fraction in ultrafiltrate from uremic sera.

An improved purification method for isolating an immunosuppressive fraction from uremic ultrafiltrates was described. Lyophilized ultrafiltrates were fractionated on Sephadex G-15 and the active fraction was further purified using high-performance liquid chromatography. The inhibitory effect of eluates on in vitro lymphocyte proliferation was assessed at the different steps of purification. Results obtained after enzyme treatment suggested that the substance(s) responsible for the immunosuppressive activity is (are) of peptidic nature. This peptide appears to be different from the other peptides previously reported, which have a much lesser activity in the lymphocyte proliferation assay.

Chromatography, Gel↗

Glycosaminoglycan chondroitin sulphate prevents loss of ultrafiltration during peritoneal dialysis in rats.

We evaluated the effect of 6 days of intraperitoneal saline infusion on peritoneal peroxidation and permeability in rats. Peroxidation of the peritoneum as measured by malondialdehyde concentration in the omentum was increased and there was a concomitant augmented membrane permeability to glucose and resulted in a loss of ultrafiltration. In vitro experiments with mesothelial cells showed that glycosaminoglycan chondroitin sulphate appears to act as a scavenger of free radicals and so protects the mesothelial cells against injury. Thus, in rats, supplementation of the infused saline with chondroitin sulphate reduces peroxidation of the peritoneum and prevents loss of ultrafiltration during peritoneal dialysis. These results suggest that chondroitin sulphate may be effective in preventing the deterioration of peritoneal permeability during chronic peritoneal dialysis. This beneficial effect probably derives from the scavenging of free radicals by chondroitin sulphate.

Animals↗

The dynamics of glomerular ultrafiltration in the rat.

Using a unique strain of Wistar rats endowed with glomeruli situated directly on the renal cortical surface, we measured glomerular capillary pressures using servo-nulling micropipette transducer techniques. Pressures in 12 glomerular capillaries from 7 rats averaged 60 cm H(2)O, or approximately 50% of mean systemic arterial values. Wave form characteristics for these glomerular capillaries were found to be remarkably similar to those of the central aorta. From similarly direct estimates of hydrostatic pressures in proximal tubules, and colloid osmotic pressures in systemic and efferent arteriolar plasmas, the net driving force for ultrafiltration was calculated. The average value of 14 cm H(2)O is lower by some two-thirds than the majority of estimates reported previously based on indirect techniques. Single nephron GFR (glomerular filtration rate) was also measured in these rats, thereby permitting calculation of the glomerular capillary ultrafiltration coefficient. The average value of 0.044 nl sec(-1) cm H(2)O(-1) glomerulus(-1) is at least fourfold greater than previous estimates derived from indirect observations.

Animals↗

Effect of mannitol on glomerular ultrafiltration in the hydropenic rat.

The effect of mannitol upon glomerular ultrafiltration was examined in hydropenic Munich-Wistar rats. Superficial nephron filtration rate (sngfr) rose from 32.0+/-0.9 nl/min/g kidney wt to 42.0+/-1.6 (P < 0.001) in eight rats. Hydrostatic pressure gradients acting across the glomerular capillary (DeltaP) were measured in glomerular capillaries and Bowman's space with a servo-nulling device, systemic (piA) and efferent arteriolar oncotic pressures (piE) were determined by microprotein analysis. These data were applied to a computer-based mathematical model of glomerular ultrafiltration to determine the profile of effective filtration pressure (EFP = DeltaP - pi) and total glomerular permeability (L(p)A) in both states. Filtration equilibrium obtained in hydropenia (L(p)A >/= 0.099+/-0.006 nl/s/g kidney wt/mm Hg) and sngfr rose because EFP increased from a maximum value of 4.2+/-1.1 to 12.8+/-0.5 mm Hg after mannitol (P <0.01). This increase was due to both increased nephron plasma flow and decreased piA. Computer analysis of these data revealed that more than half (>58%) of this increase was due to decreased piA, consequent to dilution of protein. Since EFP was disequilibrated after mannitol, L(p)A could be calculated accurately (0.065 +/- 0.003 nl/s/g kidney wt/mm Hg) and was significantly lower than the minimum estimate in hydropenia.Therefore, sngfr does increase with mannitol and this increase is not wholly dependent upon an increase in nephron plasma flow since the major factor increasing EFP was decreased piA.

Animals↗

Evidence for a parathyroid hormone-dependent influence of calcium on the glomerular ultrafiltration coefficient.

Experiments were performed on 36 plasma-expanded Munich-Wistar rats to examine the effects of acute hypercalcemia on the determinants of glomerular ultrafiltration. Elevation of total plasma calcium concentration to an average value of 13.2 +/- 0.5 mg/dl, by acute infusion of calcium chloride into nonthyroparathyroidectomized (non-TPTX) rats, resulted in significant declines in single nephron and whole kidney glomerular filtration rate. These declines were due primarily to a fall in the glomerular capillary ultrafiltration coefficient (Kf), to a mean value approximately 60% below that determined in the pre-infusion period. These changes were not seen in a separate group of sham-treated non-TPTX rats. It is of interest that these effects of acute hypercalcemia were largely abolished in rats that underwent acute TPTX before hypercalcemia. Infusion of a submaximally phosphaturic dose of parathyroid hormone, together with calcium chloride, into a second group of acute TPTX rats, however, had the effect of reproducing the striking declines in filtration rate and Kf noted in non-TPTX rats given calcium chloride alone. These findings suggest that the decline in filtration rate associated with hypercalcemia is due largely to the reduction in Kf, the latter dependent upon the presence of parathyroid hormone.

Animals↗

Respiratory drive and pulmonary mechanics during haemodialysis with ultrafiltration in ventilated patients.

The improvements of respiratory drive and pulmonary mechanics which follow haemodialysis with ultrafiltration in mechanically ventilated renal failure patients seem predictable but have not been studied before. In this study, 14 renal failure patients with stable haemodynamics mechanically ventilated with pressure support ventilation (PSV) were enrolled. Respiratory drive (represented as P0.1), pulmonary mechanics, breathing pattern, arterial blood gas and haemodynamics were measured according to the time schedule: pre-dialysis (Time 0), and at 60, 120, 180, 240 minutes thereafter. Following the removal of excess lung water during haemodialysis, auto-PEEP and patient's work of breathing (WOBp) decreased gradually. P0.1 lessened progressively along with the improvement in pulmonary mechanics. The changes in auto-PEEP and WOBp correlated closely to the pre- and post-dialysis decline of P0.1 (delta P0.1). There was a negative, moderately significant correlation between the amount of fluid ultrafiltrated during dialysis (delta UF) and the delta P0.1 (R = -0.54). The breathing pattern remained stable during dialysis. No hypoventilation or hypoxaemia occurred despite the development of metabolic alkalosis induced by bicarbonate dialysate. We have shown that respiratory drive decreases gradually during bicarbonate haemodialysis. The improvements of pulmonary mechanics, rather than the rapid alkalization of body fluids, responds to the decrease of P0.1 in renal failure patients ventilated with PSV.

Aged↗

Reverse transcriptase/polymerase chain reaction analyses of hemodialysis ultrafiltrates and sera of hepatitis C virus positive patients.

The hepatitis C virus is a highly prevalent infection among chronic dialysis patients and represents one of the major problems of hemodialysis units. Hepatitis C virus transmission occurs either by blood transfusion or nosocomially. One of the proposed pathways of nosocomial transmission of the hepatitis C virus is cross-contamination through the dialysis procedure. In an effort to elucidate whether the hepatitis C virus may pass across the hemodialysis membrane, we have performed analyses of ultrafiltrates collected in different stages of hemodialysis treatments, using different types of hemodialysis membranes and different types of dialysis machines. Samples collected from the dialysis compartment during the rinsing of the blood compartment at the end of the hemodialysis treatment were also analyzed. The hepatitis C virus was found in 17 out of 58 ultrafiltrate samples taken at different times of the hemodialysis treatment. Moreover, the hepatitis C virus was present in 15 out of 17 samples collected from the dialysate compartment during the saline solution rinsing step of the blood compartment. The presence of the hepatitis C virus had no strict correlation with the type of dialysis membrane or with the type of dialysis machine. Although the results suggest that the passage of the hepatitis C virus during the hemodialysis treatment is multi-factorial and case- specific, the most critical point is when the blood is flushed out with physiological saline.

Cross Infection↗

A mathematical model for the prediction of solute kinetics, osmolarity and fluid volume changes during hemodiafiltration with on-line regeneration of ultrafiltrate (HFR).

Hemodiafiltration with on-line regeneration of ultrafiltrate (HFR) is a technique indicated for the treatment of dialysis patients affected by inflammatory syndrome and malnutrition. In the present work, a mathematical model, which describes intradialytic fluid and solute kinetics during standard diffusive dialysis, has been adapted to analyze solutes and fluid dynamics during HFR. The model is an improved version of our previous ones, and represents a good compromise between simplicity and reliability. It considers the intradialytic kinetics of sodium, potassium and urea, and two body fluid compartments: intracellular and extracellular. Moreover, the model includes simple equations to predict the intradialytic time pattern of osmolarity. The model has been experimentally validated by using 9 HFR sessions on 9 patients (one per each patient), comparing the time course of plasma solutes and osmolarity measured every 30 minutes during HFR, with those predicted by the model. Predictions are performed a priori, i.e., without any parameter adjustment, but just starting from knowledge of a few quantities (plasma sodium, potassium, urea, osmolarity and body weight) at the beginning of the session. The average deviations between model and real data (sodium: 1.9 mEq/L; potassium: 0.32 mEq/L; urea: 1.04 mmol/L; osmolarity: 5.02 mosm/L) are of the same order as measurement errors and similar to those obtained using our previous models in standard and profiled hemodialysis. Moreover, the prediction on sodium concentration only scarcely worsens (from 1.9 to 2.02 mEq/L) if default values are used for the initial value of other solutes in blood (i.e., if the algorithm uses only initial body weight and initial sodium concentration in plasma). The results confirm the good predictive capacity of the model in HFR, and suggest its possible innovative use to optimize sodium balance in HFR, from knowledge of only the sodium concentration in the ultrafiltrate.

Aged↗

The effect of zero-balanced ultrafiltration during cardiopulmonary bypass on S100b release and cognitive function.

Zero-balanced ultrafiltration (ZBUF) might reduce the systemic inflammatory response (SIRS) during cardiopulmonary bypass (CPB) by removing inflammatory mediators. The objective of this study was to determine the effect of ZBUF on postoperative serum S100b levels, a marker of neuronal injury. In addition, the possible effects of ZBUF on postoperative neurocognitive function were assessed. Sixty patients undergoing elective coronary bypass grafting were randomly assigned either to a control group or to a protocol group in which ZBUF was performed. Serum S100b levels were measured five minutes after intubation, at the end of bypass and eight and 20 hours after arrival at the intensive care unit (ICU). Cognitive function was assessed with neuropsychological tests on the day before the operation and the sixth day after surgery. The S100b level at 20 hours after arrival at the ICU was 0.27 g/L (SD 0.16) in the control and 0.25 g/L (SD 0.12) in the group with ZBUF. There were no statistical differences at any time between the two groups. S100b was not detectable in the ultrafiltrate, indicating that these results were not obscured by washout of S100b. Thirteen patients (52%) in the control group and 14 patients (56%) in the ZBUF group showed a cognitive deficit. In conclusion, ZBUF during CPB does not decrease the release of S100b. This result is not affected by washout. ZBUF did not reduce the incidence of early neurocognitive deficits. The role of SIRS in the development of cognitive dysfunction following CPB remains to be resolved.

Aged↗

Does modified ultrafiltration reduce the systemic inflammatory response to cardiac surgery with cardiopulmonary bypass?

Cardiopulmonary bypass (CPB) is associated with an accumulation of total body water and a systemic inflammatory response syndrome (SIRS), which, in turn, is associated with organ dysfunction and postoperative morbidity. It has been suggested that modified ultrafiltration (MUF) may be capable of reducing SIRS and improving clinical outcome by filtering out the inflammatory mediators generated during CPB. This paper reviews the data regarding the use of MUF in paediatric and adult settings. Specifically, three issues will be considered: 1) Does MUF improve clinical outcome? 2) Does MUF reduce the systemic inflammatory response to cardiac surgery with CPB? 3) Is MUF more effective than conventional ultrafiltration in improving clinical outcome?

Cardiopulmonary Bypass↗

Effects of positive end-expiratory pressure ventilation and extracorporeal ultrafiltration method in patients with refractory heart failure.

We studied the effects of positive end-expiratory pressure (PEEP) ventilation in ten patients with acute myocardial infarction (nine in Killip class III, one in Killip class IV; pulmonary capillary wedge pressure greater than 24 mmHg) and of extracorporeal ultrafiltration method (ECUM) in seven patients with refractory heart failure due to acute myocardial infarction and others. Application of PEEP resulted in significant increases in PaO2 and SaO2 and decrease in PaCO2. Significant reduction in mean pulmonary arterial and pulmonary capillary wedge pressures and heart rate was observed, while stroke work index increased significantly. There was a significant correlation between changes in stroke work index and PaO2 after the application of PEEP. The use of ECUM removed fluid of 1416 +/- 662 ml (680-2800 ml) with the ultrafiltration flux rate being 478 +/- 223 ml/hour. Significant decreases in mean pulmonary arterial, pulmonary capillary wedge and central venous pressures were observed, while PaO2 increased significantly. BUN and serum creatinine levels increased significantly, and total protein and serum albumin tended to increase. There was a significant correlation between fluid removed and change in PaO2 after the use of ECUM. Thus, PEEP and ECUM are beneficial for patients with refractory heart failure. The mechanism(s) are: reduction in preload due to an increased intrathoracic pressure and a decreased systemic venous return with PEEP, or due to removal of excess fluid with ECUM, and improvement of the oxygenation of the blood.

Aged↗

Effect of intravenous saline, albumin, or hydroxyethylstarch on blood volume during combined ultrafiltration and hemodialysis.

It is generally advocated to use saline or albumin infusions during symptomatic hypotension during dialysis. However, because of their side effects and/or costs, they are of limited use. Hydroxyethylstarch (HES), a synthetic colloid with a long-standing volume effect, is used in the management of hypovolemia. In this study, the efficacy of three fluids (isotonic saline [0.9%], albumin [20%], and HES [10%]) was assessed during three treatment sessions with combined ultrafiltration and hemodialysis, which differed in the type of fluid given intravenously. Changes in relative blood volume (BV), systolic BP (SBP), and vascular reactivity (venous tone [VT]) were compared. An intravenous infusion of 100 ml of fluid was given when the decrease in BV versus baseline was more than 10% as measured by a continuous optical reflection method. The ultrafiltration was continued. BV decreased significantly versus baseline independent of the intravenous fluid administration in all three treatment sessions. However, when we compared BV values at the end of the dialysis session with those at the time of infusion, BV continued to decrease significantly with saline (change in BV -4.56 +/- 2.75%; P < 0.05) and albumin (change in BV -2.13 +/- 2.51%; P < 0.05), but not with HES (change in BV -0.15 +/- 2.17%; NS). Between albumin and HES there were no significant differences in changes in BV (NS), whereas between HES and saline (P < 0.05) and between albumin and saline (P < 0.05) the differences in BV changes were significant. SBP remained unchanged within each session. Although SBP tended to decrease more with saline compared to albumin and HES, the difference was not significant. The higher decrease in BV and SBP with saline was counterbalanced by a significantly higher increase in VT, while VT remained unchanged in the other two sessions. It is concluded that HES is a promising fluid in preserving blood volume, comparable to albumin, but superior to saline.

Adult↗

Ultrafiltration and alumina adsorption of micelles for the preconcentration of copper(II) in water.

Micellar-enhanced ultrafiltration was considered from the viewpoint of trace analysis, by taking copper(II) as an example. Copper(II) cations were collected electrostatically on micelles of sodium dodecyl sulfate, and separated from the mother liquor by ultrafiltration. However, the final solution contained a large amount of surfactant, which caused serious interference in the determination. This problem was overcome by using alumina adsorption, where negatively charged micelles were adsorbed on positively charged alumina particles and then recovered by conventional filtration. The copper was leached from the micelles with 4 mol l(-1) nitric acid, leaving the surfactant on the alumina. The proposed method was successfully applied to an analysis of certified reference water samples.

Journal Article↗

Discriminative impact of ultrafiltration on peritoneal protein transport.

OBJECTIVE: The dialysate concentration of large proteins increases, on average, linearly during the whole peritoneal dialysis dwell, and this linear pattern seems to be independent of the rate of ultrafiltration induced by dialysis fluid. However, we observed a high variability of protein kinetics in individual dwell studies. Therefore, we studied the details of the kinetic pattern of peritoneal transport. DESIGN AND METHODS: Kinetics of beta2-microglobulin, albumin, and total protein was examined in 23 clinically stable continuous ambulatory peritoneal dialysis patients using Dianeal 3.86% (15 dwell studies) or Dianeal 1.36% (9 dwell studies) dialysis fluid. Dialysate volume was measured using radioisotopically labeled albumin as a volume marker, with corrections for sample volume and absorption of fluid and marker from the peritoneal cavity. The generalized version of the Babb-Randerson-Farrell model was applied to estimate diffusive mass transport coefficient (K(BD)) and sieving coefficient (S) for proteins and small solutes (urea, creatinine, glucose, sodium, potassium). To quantify deviations from the linear pattern of protein dialysate concentration increase, the ratio (SR) of the slope of the linear regression line for the initial 3-30 minutes, divided by the slope for the next 60 - 360 minutes, was evaluated for albumin. RESULTS: In 5 dwell studies with Dianeal 3.86% fluid, SR was lower than 1 [low albumin transport (LAT) group, median SR = 0.49, range -4.39 - 0.71], while in the other 10 dwell studies with this solution, SR was higher than 1 [high albumin transport (HAT) group, median SR = 2.77, range 1.32 - 7.56]. Clearances of albumin up to 120 minutes were higher in the HAT group than in the LAT group. The transport of fluid, beta2-microglobulin, and small solutes did not differ between the LAT and the HAT groups. K(BD) values for proteins did not differ between the groups, but S values for albumin and total protein were lower for the LAT group than for the HAT group. A similar diversity was found in the dwell studies with Dianeal 1.36%: In three dwell studies, SR for albumin was lower than 1 (median SR = 0.95, range 0.70 - 0.97), and in six dwells it was higher than 1 (median SR = 1.55, range 1.23 - 1.98). In general, the SR values observed with Dianeal 1.36% were closer to 1 than those for Dianeal 3.86%. CONCLUSIONS: Ultrafiltration may affect the initial kinetic patterns of large protein (such as albumin) transport in two opposing ways: (1) by slowing the increase of protein concentration in dialysate (due to a low sieving coefficient, LAT group), and (2) by speeding up the increase of protein concentration in dialysate (due to a high sieving coefficient, HAT group). The average pattern in a non-selected group of studies is, however, close to a steady (linear) increase.

Albumins↗

[The clinical use of blood ultrafiltration in leptospirosis patients with acute kidney and liver failure].

The use of ultrafiltration of blood in clinical settings in the treatment of patients with leptospirosis presenting with acute renal failure permits enhancing a detoxicating effect due to elimination with the ultrafiltrate of up to 30% of products of nitrogenous metabolism. This allows the water balance to be corrected, homeostasis, the functional activity of the cardiovascular, respiratory systems to be stabilized. Therapeutic effectiveness is enhanced that is evidenced by a 20% decline in the incidence of complications and in case-fatality rate in grave forms of leptospirosis.

Acute Kidney Injury↗

Encapsulating peritoneal sclerosis: definition, etiology, diagnosis, and treatment. International Society for Peritoneal Dialysis Ad Hoc Committee on Ultrafiltration Management in Peritoneal Dialysis.

Current definitions of encapsulating peritoneal sclerosis are practical and clinically relevant. It is important to adhere to a more uniform use of the proper terminology, and it is the recommendation of the authors that EPS be adopted as the more appropriate term. The best literal definition of EPS is based on clinical-pathologic criteria. Differentiation of EPS from the general category of ultrafiltration failure is required. Further, better appreciation of the diverse pathways that can lead to the same final common clinical-pathologic picture should not be overshadowed by the requirement of uniform terminology. Incidence and prevalence of the syndrome have been defined in some large populations and a few single-center experiences. The former show an incidence of less than 1%, while higher percentages are reported in the latter. The reported increased incidence with duration on therapy requires validation. The epidemiology of the syndrome offers limited insight into its pathogenesis. A list of factors, both dialysis-related and non dialysis-related. has been accumulated. Except in a few categories where agents are clearly related to the development of EPS, the majority of the listed factors for dialysis-related BPS remain, at best, associations and at worst, simple conjecture. The same limitations that plague the issue of etiology apply in the area of pathogenesis. More basic, focused work is required. The diagnosis of EPS remains based on clinical suspicion confirmed with, primarily, radiologic findings. Pathologic confirmation is obtained in cases that come to surgery for management or for catheter removal. Radiologic studies are precise enough for confirmation, but none have been evaluated for early diagnosis for possible early intervention or prevention. Studies based on transport characteristics or effluent dialysate constituents are not useful for EPS. At present, there are no reliable predictive tests for BPS that can be used in individual patients. Therapy of BPS is based on anecdotal evidence. The possible variable etiologies and probable distinct pathways leading to the syndrome may make a uniform therapeutic approach unlikely. Further, the limited number of cases and the sporadic pattern of occurrences make therapeutic trials not readily feasible. This is distinct from the case of ultrafiltration failure, where significant advances in mechanism elucidation and rationale-based interventions have been made.

Humans↗

[Milk ultrafiltrate as a promising source of angiogenin].

The use of membrane technologies in the production of soft cheese (children's food) is associated with the appearance of up to 80% of angiogenin in the ultrafiltrate. An electrophoretically homogeneous preparation of angiogenin (MW approximately 17 kDa) was obtained from milk ultrafiltrate by two-stage ion-exchange chromatography. The yield of the angiogenin was approximately 60%, which corresponds to a 586-fold purification of the raw material. The obtained preparation retained stability in the course of lyophilization and could be stored at 4 degrees C for a long time without decomposition.

Angiogenesis Inducing Agents↗

Polyurethane and sulfonated polysulfone blend ultrafiltration membranes. I. Preparation and characterization studies.

Polyurethane (ether type) and sulfonated polysulfone (sodium salt form) in the presence of polyethylene glycol 600 were blended in various compositions using N,N'-dimethylformamide as solvent and used for preparing ultrafiltration membranes by the phase inversion technique. Polymer blend composition, additive concentration, and casting and gelation conditions were optimized. Blend membranes were subjected to ultrafiltration characterizations such as compaction, pure water flux, water content, and membrane resistance. The membranes were also subjected to the determination of pore statistics and molecular weight cutoff determination studies using dextran of different molecular weights. Surface morphology of the membranes was analyzed using scanning electron microscopy at different magnifications. The effects of polymer composition and additive concentration on the above parameters were analyzed and the results are compared and discussed with those of pure sulfonated polysulfone membranes. The derived pore size, porosity, and number of pores have a remarkable interrelationship and also have a definite role and relationship with the molecular weight cutoff, morphology, and flux performance of the membranes.

Journal Article↗