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3H-inulin and electrolyte concentrations in Bowman's capsule in rat kidney. Comparison with artificial ultrafiltration.

Micropuncture experiments were performed on Bowman's capsules in male and female non-diuretic Munich rats. 55 samples were collected and analysed for Na, Cl, K, Ca, P, Mg and 3H-inulin contents. Their electrolyte concentrations were compared to the corresponding concentrations obtained from plasma artificial ultrafiltrates. Compared to normal Wistar rats, our Munich rats had several special characteristics: high arterial pressure (115-155 mm Hg), high concentrating ability (phi equals 2684 mOsm/1) and high NaCl reabsorption capacity. Whole kidney GFR was low in males (0.361 ml/min/kidney/100 g B.W.). 3H-Inulin concentration was the same in plasma and glomerular ultrafiltrates (GF). The corresponding ratio (GF/P) in equals 1.03 plus or minus 0.01 (N equals 55) confirmed the lack of sieving effect for inulin. GF electrolyte concentrations were, for Na, Cl, K, Ca, P, Mg respectively 139 plus or minus 0.05, 1.46 plus or minus 0.07 and 0.52 plus or minus 0.04 ml/1 (N equals 23) in females and 141 plus or minus 2, 120 plus or minus 2, 3.84 plus or minus 0.07, 1.31 plus or minus 0.03, 1.78 plus or minus 0.05 and 0.48 plus or minus 0.01 mM/1 (N equals 32) in males. Comparison of ultrafiltration trough a cuprophan membrane and glomerular ultrafiltration led to the following conclusions: For Na, Cl and P artificial and glomerular ultrafiltration produced identical results. On the other hand, for Ca and to a lesser extent for Mg and K ions, artificial ultrafiltration did not accurately reflect the true glomerular ultrafiltrate composition. The reasons for these differences are discussed below.

Animals

Comparison of polymer, glucose, and hydrostatic pressure induced ultrafiltration in a hollow fiber dialyzer: effects on convective solute transport.

Ultrafiltration induced by (1) poly(sodium acrylate), (2) glucose, and (3) hydrostatic pressure was studied in a hollow fiber dialyzer. Poly(sodium acrylate) added to dialysate induced large amounts of ultrafiltration without crossing the dialyzer membrane. Sodium ions of the acrylate polymer were osmotically active but were held in dialysate by the impermeant anionic polymer. The hydrostatic pressure equivalent of osmotic pressure induced primarily by the sodium ions approximated that predicted for a completely impermeant molecule. The apparent (net) sieving coefficients for vitamin B12 observed during polymer and hydrostatic ultrafiltration studies were both significantly higher than that observed during glucose ultrafiltration but did not differ from each other. These studies suggest that sodium salts of polyanions can provide an osmotic driving force to yield large amounts of ultrafiltration in dialysis systems and yet not cross the membrane. The studies also suggest that relatively less efficient convective transport with glucose as compared to hydrostatic pressure is neither a membrane phenomenon nor a characteristic of all osmotic pressure induced ultrafiltration. Relatively low effective solute sieving appears to be associated with osmotic induced ultrafiltration with a permeant solute. Under such conditions it is proposed that molecular interaction within the membrane impairs convective transport.

Acrylic Resins

Theoretical aspects of various ultrafiltration methods in artificial kidney therapy.

A mathematical model including urea, creatinine and other osmotically important solutes (such as sodium, potassium and chloride) is applied to calculate volume shifts, caused by ultrafiltration, between the fluid compartments of the body. The volume shifts between the intracellular (ICV) and the extracellular (ECV) compartments are mainly caused by alteration of extracellular sodium concentration. Various methods of achieving ultrafiltration, including conventional dialysis, initial ultrafiltration using Cuprophan (without dialysis) or hemofiltration, produce different responses. In choosing a method, one must consider that both a rapid decrease of ECV and a fast shift of water from ICV to ECV should be avoided. In pure hemofiltration, ultrafiltrate is isotonic and water is removed from ECV only. Hemofiltration with dilution produces a very slow shift of water between ICV and ECV dependent on sodium concentration of plasma and diluting fluid. In initial ultrafiltration through Cuprophan, water is shifted from ICV to ECV. With ultrafiltration throughout the entire dialysis, there are pronounced shifts between ICV and ECV dependent on the difference of the sodium concentration between plasma and dialysate.

Biological Transport, Active

Growth of human diploid cells (strain MRC-5) in defined medium; replacement of serum by a fraction of serum ultrafiltrate.

A calf serum ultrafiltrate fraction permitted growth for at least 3.5 generations, including one subculture, of MRC-5 cells in defined medium in the absence of whole serum. The active material has a molecular weight of 10 000 Daltons or less. This suggests that there may be no requirement for a large macromolecular component of serum. The ultrafiltrate was assayed by maximum cell yield from a serum-limited inoculum in a defined medium containing non-limiting amounts of vitamins, amino acids, glucose, a 68-component supplement, iron and methylcellulose. The levels of vitamins, amino acids and glucose were based on quantitative measurements of uptake and the levels of the other components by minimum amount required for maximum yield in defined medium without ultrafiltrate or serum. With excess ultrafiltrate maximum cell yield was limited by the defined part of the medium, probably the supplement. The cell doubling time in defined medium with ultrafiltrate fractions was 70 h compared with 27 h in the medium with serum. Excess ultrafiltrate did not inhibit growth. The lowered growth rate is attributed to a nutritional deficiency in the supplement.

Blood

Binding of 63Ni (II) to ultrafiltrable constituents of rabbit serum in vivo and in vitro.

Binding of 63Ni(ll) to ultrafiltrable constituents of rabbit serum was studied (a) after in vitro incubation (2 h, 37 degrees C) of rabbit serum with 63NiCl2 (10-100 mumol/liter), and (b) at intervals (0.25-2 h) after in vivo administration of 63NiCl2(40-160 mumol/kg body wt,i.v.). Serum ultrafiltrates were fractionated by thin-layer chromatography, and the separated compounds made visible by autoradiography and by ninhydrin staining. Severel (congruent to 5) ultrafilitrable 63Ni-complexes were demonstrable as distinct radiodense 63Ni-bands with chromatographic mobilities corresponding to those of ninhydrin-positive bands. Unbound 63Ni(ll) was not detected in serum ultraviltrates in either the in vitro or in vivo experiments. In sera (n equals 10) incubated in vitro with 63Ni(ll) (10 mumol/liter), the mean percentage of ultrafiltrable 63Ni was 36% (range equals 33-38) of total serum 63Ni. In contrast, in sera (n equals 10) obtained 2 h after i.v. injection of 63Ni(ii) (40 mumol/kg), the mean concentration of total serum 63Ni was 10.8 mumol/kg), the mean concentration of total serum 63Ni was 10.8 mumol/liter (ranger equals 6-14), and the mean percentage of ultrafiltrable 63Ni was 15% (range equals 9-21) of total serum 63Ni. The disparity between the percentages of ultrafiltrable 63Ni obtained in vitro and in vivo was obviated when the in vivo experiments were performed in rabbits bilaterally nephrectomized, with ligated common bile ducts. This investigation confirms the existence of several nickel receptors in serum ultrafilitrates and substantiates the role of ultrafiltrable complexes in the excretion of nickel.

Amino Acids

Separation of dialysis and ultrafiltration-does it really help?

Ultrafiltration alone for fluid removal has been used and assessed in a number of clinical studies. A paired study of ultrafiltration alone against haemodialysis has shown that as compared to haemodialysis, ultrafiltration alone within the ultrafiltration rates used is well tolerated. The use of ultrafiltration alone for both acute and chronic fluid overload has been shown to be an ideal therapeutic procedure. In a third study using the Rhodial 75 system and RP6 dialyser in a group of non-fluid-overloaded patients the separation in time of ultrafiltration from haemodialysis has shown no obvious advantages over regular haemodialysis.

Adult

Hemodynamic changes during sequential ultrafiltration and dialysis.

Seven patients on regular dialysis were studied to elucidate the hemodynamic changes during ultrafiltration and dialysis, performed sequentially, the period of ultrafiltration (1 hour) either preceding or following dialysis (3 hours). During dialysis ultrafiltration was prevented by applying positive pressure in the dialysate compartment. Cardiac index (dye dilution: indocyanine green), heart rate, stroke volume index, blood pressure, and total peripheral vascular resistance index were measured. During ultrafiltration, cardiac index and stroke volume index decreased, but heart rate was not significantly changed. Total peripheral vascular resistance increased, resulting in unchanged blood pressure. During dialysis, the total peripheral vascular resistance decreased, but cardiac index and heart rate increased. BP decreased when the increase in cardiac index was insufficient to compensate for the decrease in total peripheral vascular resistance. PRA increased during ultrafiltration due to hypovolemia and decreased during dialysis, presumably due to decreased sympathetic activity which may also be a cause of dialysis-induced vasodilation.

Adult

[Hydrolyzed lactose contained in the ultrafiltrate of milk or milk products in an enzymatic membrane reactor].

Milk and milk by-products with a low lactose content, very interesting from a nutritional and technological point of view, were obtained by the application of the enzymatic membrane reactor technique. A previous separation of the aqueous phase of milk or ultrafiltrate was necessary and realized by ultrafiltration. The enzyme, a commercial beta-galactosidase, was maintained in solution in the retentate part of the membrane reactor. The optimal conditions of the lactose hydrolysis in milk and whey ultrafiltrates were determined. The behaviour of the aqueous phase of milk in membrane reactor, specially of mineral salts, was studied. Three possibilities were proposed to avoid a calcium-phosphate deposit on the surface of (and in) the reactor membranes: a precipitation of calcium salts by heating, a partial demineralization by electrodialysis or ion exchange, a calcium complexation by addition of sodium citrate. A continuous process for the lactose hydrolysis of milk and demineralized whey or milk ultrafiltrate was proposed. The organoleptic quality of low lactose milk, before and after heat treatment, was evaluated by a tasting panel. High sweeting syrup, were obtained by concentration of lactose hydrolyzed and demineralized ultrafiltrates. Nutritional aspects of these products are discussed specially from the toxicological point of view of galactose.

Animals

Human transfer factor prepared by dialysis, ultrafiltration and gel chromatography: biological activity in local transfer of skin sensitivity.

Human transfer factor (TF) was prepared by a variety of methods including dialysis using cellophane tubing, ultrafiltration through a membrane of known pore size. Sephadex G25 chromatography or combinations of some of these methods. In general the various preparations when injected locally into human skin gave greater delayed-type responses than antigen (PPD or Candida) alone. The combination of either vacuum dialysis, or ultrafiltration, with G-25 chromatography gave as good or better TF activity when compared with unchromatographed materials. Since ultrafiltration and concentration is rapid procedure and eliminates the need for freeze-drying, in contrast to vacuum dialysis against water, these results indicate that ultrafiltration and G-25 chromatography provide a convenient method for preparing large batches of relatively pure TF from leucocyte extracts.

Antigens, Fungal

Clinical evaluation of a pre-set ultrafiltration rate controller available for single pass and hemodiafiltration systems.

Introduction of high flux-type dialyzers, such as the RP-6, makes it necessary to devise an ultrafiltration rate controller for a single pass system. For this purpose, a new pre-set ultrafiltration rate controller has been developed and examined experimentally and clinically. The controller has twin chambers, each of which is divided into two symmetrical parts by a vertically-placed diaphragm. The diaphragm shifts repeatedly from right to left, aspirating in and driving out fresh or used dialysate alternately. If one removes a certain amount of used dialysate from a branch of the efferent line, negative pressure develops and aspirates an equal amount of water from the dialyzer. Therefore, extra dialysate obtained by a pump precisely reflects ultrafiltration rate. The controller has been used on five patients. The scheduled ultrafiltration rate was easily obtainable. The apparatus is also available for hemodiafiltration. Initial clinical trial has been promising.

Body Fluids

Influence of ultrafiltration on plasma renin activity and adrenergic system.

The influence of efficient ultrafiltration without dialysis fluid was compared to the standard dialysis technique in two groups of 4 patients with chronic renal failure on maintenance haemodialysis. Supine plasma renin activity (PRA), plasma concentration of noradrenaline (NA), and adrenaline (A) and the Valsalva manoeuvre were determined before and after the period of ultrafiltration at the beginning and at the end of the experiment. The behaviour of these parameters was related to changes of blood pressure and body weight. The rapid weight loss was well tolerated during ultrafiltration only, with a significant increase of plasma catecholamines concentration; in contrast, patients treated with ultrafiltration and dialysis showed no significant increase of NA and A levels and they frequently became hypotensive. No relationship was observed between changes in PRA and those in body weight and blood pressure. Our data suggest that rapid removal of catecholamines during standard dialysis hinders the compensatory increase of the adrenergic activity and is responsible for hypotension.

Blood Pressure

A simple method for incorporating single pass dialysate delivery and controlled ultrafiltration with the RP-6 high flux dialyzer.

A simple hemodialysis protocol has been developed to permit significant "middle molecule" clearance, yet retain normal low molecular weight clearance. The high flux RP-6 dialyzer has been combined with a single pass dialysate delivery system to provide accurate control of ultrafiltration without resorting to specialized or expensive equipment. By operating the RP-6 in the co-current mode, a simple valve on the dialysate output can be used to regulate ultrafiltration. At QB = 200 ml/min and QD = 500 ml/min, CU = 127 ml/min and CB12 = 56 ml/min at zero ultrafiltration rate; these values increase considerably with ultrafiltration. This protocol offers dialysis centers with standard equipment the opportunity to use high flux membranes in a routine manner.

Animals

Performance and clinical use of a convertible hemodialysis (HD) - ultrafiltration (UF) system.

A hemodialysis-ultrafiltration system has been developed and evaluated. It may be used either as a conventional hemodialyzer or as a nondialytic ultrafilter. When used as a dialyzer an ultrafiltration controller is required to fix ultrafiltration rate at the desired level. Rates of low molecular solute removal are compatible with those observed in commercially available artificial kidney systems, higher clearances are obtained for middle molecules, and the rate of ultrafiltration can be controlled within narrowly prescribed limits.

Blood Flow Velocity

Experience with a low volume ultrafiltration cell in small children*.

A low volume (16 ml) ultrafiltration cell was used ten times in two small, fluid overloaded children to remove plasma water. The device was simple to use and, at slow blood flow rates (25-50 ml/minutes) and low transmembrane pressures (10-30 mm Hg), provided controlled removal of excess fluid. Although no major complications were encountered, hypothermia and hypotension (at ultrafiltrate flux rates exceeding 0.5 ml/kg/minute) were observed. The ultrafiltrate solute concentration was similar to plasma and no significant shifts in serum electrolytes were induced. The ultrafiltrate protein concentration of 64 to 2,760 mg/dl was much higher than previously reported.

Blood Flow Velocity

[Hemodynamic changes during ultrafiltration and hemodialysis in uremia].

1. The ultrafiltration causes a reduction of blood pressure and minute output of the heart which is compensated by vasoconstriction and thus a decrease of blood pressure is prevented. 2. Changes in the salt concentrations with reduction of the osmolarity during the dialysis without simultaneous ultrafiltration lead to vasodilation and hypotension despite increase of the minute output of the heart. 3. During a usual haemodialysis (i.e. dialysis with simultaneous ultrafiltration) the vasodilating effect of the dialysis may abolish the vasoconstrictive effect of the ultrafiltration and thus may be the cause of the hypotension.

Adult

Ultrafiltration without dialysis for removal of fluid and solutes in uremia.

A review is presented of the use of sequential ultrafiltration and dialysis to facilitate asymptomatic fluid removal in dialysis patiens, and the use of ultrafiltration as a method to remove uremic compounds. In sequential ultrafiltration and dialysis, the two physical principles in hemodialysis are separated in time. Hypotension and other side-effects which may be encountered when the two procedures take place simultaneously are eliminated or minimized by sequential treatment. Hemofiltration is an entirely new form of treatment, which mimics the performance of the human kidney better than hemodialysis. The blood is purified by ultrafiltration and fluid replacement either before or after the ultrafilter device. Preserved well-being or improvement in clinical condition have been reported after prolonged treatment with hemofiltration in spite of relatively inefficient elimination of small molecules as urea and creatinine. The most consistent beneficial effect of hemofiltration appears to be better blood pressure control in severely hypertensive patients than with conventional hemodialysis.

Humans