Effects of internal filtration on the solute removal efficiency of a dialyzer

To improve solute removal efficiency, several types of dialyzers with enhanced internal filtration were introduced for clinical application. In these dialyzers, enhanced internal filtration increased convective transport of the solute, in addition to diffusive transport. In this study, the effects of internal filtration on solute removal efficiency were examined by both analytic and experimental studies. Internal filtration is affected by blood (Q(B)) and dialysate (Q(D)) flow rates; the patient's hematocrit and plasma level of total protein; and the effective length (L(eff)), inner diameter (D), and density ratio (DR) of the hollow fibers. An analytic model was introduced for the estimation of the changes in mass and momentum along the dialyzer. It clarified the effects of these parameters on maximum internal filtration flow rate (Q(IF)) and clearance (K) of urea (60 daltons), vitamin B(12) (1,355), and myoglobin (17,000). As a result of the analytic study, Q(IF) was increased, resulting in a smaller D, a longer L(eff), and a larger DR value. Several types of dialyzers with the same cellulose triacetate membrane, produced by Toyobo Co, Ltd., Ohtsu, Japan, and Nissho Corporation, Kusatsu, Japan, were used for the experimental study. An in vitro evaluation using myoglobin solution showed the same trends as found in the analytic study. For example, a dialyzer with 150 microm of D has a 72.0 ml/min myoglobin K value, much higher than that of 53.7 ml/min for a dialyzer with 200 microm of D under constant Q(B) (300 ml/min) and DR (50%) values. Development of a dialyzer with enhanced internal filtration, however, should take the patient's safety into account, and hemolysis and endotoxin invasion from the dialysate to the patient should be avoided.     

Effect of blood flow rate on internal filtration in a high-flux dialyzer with polysulfone membrane

Internal filtration/backfiltration (IF/BF) of a dialyzer depends on several parameters. This study evaluated the effect of the blood flow rate (Q (B)) on the internal filtration flow rate (Q (IF)) measured using Doppler ultrasonography for a high-flux dialyzer with a polysulfone membrane, APS-15E. In an in vitro study, bovine blood was circulated through the dialyzer, at a Q (B) of 100-350?mL/min. The clearances (CL) of creatinine, β(2)-microglobulin, and α(1)-microglobulin were then investigated. Q (IF) increased with the Q (B) value. A good correlation was obtained between Q (IF) and the pressure difference between the pressures at the inlet of the blood compartment and the pressure at the outlet of the dialysate compartment. The creatinine CL values strongly depended on Q (B) because molecular diffusion was dominant. The β(2)-microglobulin CL also depended on Q (B), because its removal rate seemed to be affected by both diffusive and convective transport caused by the IF/BF. An extremely low CL value was obtained for α(1)-microglobulin because of its low diffusivity and membrane fouling induced by proteins plugging the membrane. In conclusion, the IF/BF in the dialyzer strongly depends on Q (B). Furthermore, the dependence of the solute clearance on Q (B) decreased with increasing molecular size of the solute because of the decrease in diffusivity through the membrane.     

Doppler ultrasound wall removal based on the spatial correlation of wavelet coefficients

In medical Doppler ultrasound systems, a high-pass filter is commonly used to reject echoes from the vessel wall. However, this leads to the loss of the information from the low velocity blood flow. Here a spatially selective noise filtration algorithm cooperating with a threshold denoising based on wavelets coefficients is applied to estimate the wall clutter. Then the blood flow signal is extracted by subtracting the wall clutter from the mixed signal. Experiments on computer simulated signals with various clutter-to-blood power ratios indicate that this method achieves a lower mean relative error of spectrum than the high-pass filtering and other two previously published separation methods based on the recursive principle component analysis and the irregular sampling and iterative reconstruction, respectively. The method also performs well when applied to in vivo carotid signals. All results suggest that this approach can be implemented as a clutter rejection filter in Doppler ultrasound instruments.     

Improvement in Doppler ultrasound human foetal heart rate records by signal correlation

An improved method for the determination of foetal heart rate from Doppler ultrasound signals is described and evaluated. It determines the most probable pulse interval from the recurrence times of multiple echoes generated by each cardiac pulse. The method, when optimised, is shown to offer an improvement over current systems, especially in reduced signal loss.     

Effect of pulsatile arterial diameter variations on blood flow estimated by Doppler ultrasound

High-resolution measurements of common carotid and femoral arterial diameters have been performed by ultrasound echo devices. When combined with pulsed Doppler measurements of cross-sectional averaged velocity in the same vessels, exact calculations of flow were made possible. The median peak-to-peak pulsatile diameter variations were 0.19 mm (2.8 per cent) in the femoral artery and 0.49mm (6.7 per cent) in the common carotid artery. Flow values were calculated either by taking the time-averaged diameter as a constant value, or by taking into account the dynamic variations in diameter. In comparing the two values, a quantification of the magnitude of error introduced by the averaging of the diameter was made possible. An error in the range 1.5–3.8 per cent was found for the femoral artery, whereas the error in the common carotid artery was in the range 0.4–3.6 per cent despite the larger amplitude of the pulsations in this vessel.     

Rapid removal of heparin from plasma by affinity filtration

Coagulation test abnormalities caused by the presence of heparin are not uncommon and frequently result in additional laboratory investigation and unwarranted therapy. Methods to neutralize the effect of heparin include the addition of polyanions, enzymes, or resins to the clinical samples. These techniques are time consuming and cumbersome and produce inconsistent results. As an alternative, use of a positively charged porous filtration medium to remove heparin from the sample is described. The filtration procedure requires less than one minute and provides a consistent and total removal of heparin at plasma concentrations in excess of therapeutic levels. Chromogenic substrate analysis for residual heparin activity confirms total removal of the drug at levels greater than one unit/mL of plasma. In clinical trials, filtration normalized the activated partial thromboplastin time (APTT) of all patient specimens containing heparin (n = 41). Filtration did not shorten the coagulation assay times of patients receiving warfarin (n = 36) or of those with a variety of acquired coagulopathies (n = 14). The level of coagulation factors adsorbed to the filter medium compares favorably to that adsorbed by other commercially available heparin-binding resins. Routine use of the filter in the clinical laboratory allows for the rapid and definitive identification of heparin in specimens with prolonged coagulation times and provides clinically meaningful data.     

Effect of chronic sympathetic denervation upon the transcapillary filtration rate induced by venous stasis

The effect of venous pressure elevation upon capillary filtration rate in the limb was studied in 6 chronically sympathectomized patients. Five healthy subjects served as controls. Volume changes of the forearm or calf were recorded by a strain-gauge plethysmograph. Relative blod flow in subcutaneous and muscle tissue during venous stasis was measured by the local ¹³³Xe washout technique. In the denervated limbs there was a linear relationship between net capillary filtration rate and venous pressure elevation. In the controls a non-linear relationship was seen as venous pressure elevation of 40 mmHg only caused an increase in net filtration rate of about 66% of that expected from a linear relationship. In the denervated limbs blood flow in muscle and subcutaneous tissue remained constant during venous pressure elevation of more than 30 mmHg whereas in the non-denervated limbs blood flow decreased by about 50% in both tissues. The results suggest that a local sympathetic veno-arteriolar (axon) reflex plays a dominant role for the reduced increase in net capillary filtration rate during large increases in venous pressure. The local axon reflex may therefore act as an edema protecting factor.     

Effect of furosemide on local and zonal glomerular filtration rate in the rat kidney

Furosemide has been reported to produce disproportional changes in blood flow in cortical zones and to inhibit tubuloglomerular feedback (TGF), suggesting that furosemide might alter the intracortical distribution of glomerular filtrate. We have tested this hypothesis by a new method for measuring local and total glomerular filtration rate (GFR) based on proximal tubular accumulation of the basic polypeptide aprotinin (mol wt 6513). Local GFR was calculated in tissue samples dissected from outer cortex (OC), inner cortex (IC) and the corticomedullary border zone (CM) from the plasma clearances of two aprotinin tracers injected i. v. before and after a 3 min i. v. infusion of 25 mg kg^-1 furosemide. The mean of five samples from each region was used to determine zonal GFR. Isotonic saline was infused at a rate corresponding to urine flow. Furosemide reduced whole kidney GFR from 1.17 to 1.00 mL min^-1 and gave a similar reduction of renal artery blood flow. Urine flow increased from 0.6 to 17% of GFR. Haematocrit (? 0.48) and plasma protein concentration (? 55 mg mL^-1) were maintained while the arterial blood pressure tended to decline (118pL5 mmHg to 108pL6 mmHg, P < 0.05). GFR in OC, IC and CM (1.58, 1.18, 0.42 mL min^-1 g^-1) fell to 87, 88 and 88% of control after furosemide infusion respectively. The furosemide/control ratio for each sample showed a coefficient of variation of about 3%. We conclude that furosemide produced a modest GFR reduction that was uniform throughout the renal cortex. The homogenous GFR response suggests a similar TGF constriction tone in preglomerular vessels of deep and superficial nephrons.     

Adsorption of lipase on hollow fiber membrane chips

The amount of lipase from Mucor miehei adsorption on ultrafiltration polysulfone hollow fiber membrane chips has been determined using different lipase concentrations at three different temperatures, namely 30, 35, and 40 degrees C. It was experimentally shown that adsorption of lipase increases with temperature. The results were used to evaluate the constants found in the Langmuir adsorption isotherm model coupled with the Van't Hoff's relationship. A temperature dependence correlation for the amount of adsorbed lipase activity, alip,ads, and that present in the supernatant solution, alip,free was determined. The effect of varying the concentration on a cross-linking agent, namely, glutaraldehyde, to the membrane chips was also tested. It was found that, under the same operating conditions, the amount of lipase adsorbed on polysulfone membranes was increased dramatically after pre-treating the membrane with 1% Glutaraldehyde. However, increasing the concentration of the cross-linking agent has a low effect on the amount of lipase adsorbed.     

Effect of papillary exposure on intrarenal distribution of glomerular filtration rate and of plasma flow

Removal of the renal pelvis in order to expose the renal papilla has been shown to cause impairment of the renal concentrating ability by an unknown mechanism. To study this phenomenon, urine osmolality (Uosm), single-nephron glomerular filtration rate (SNGFR) in outer and inner cortical nephrons and the inner and outer medullary plasma flow were determined. Measurements were performed on groups of rats before (control) and 15, 45 and 90 min after exposure of the left renal papilla. Rats with an intact ureter were studied in parallel to see whether the variables varied within the 90-min period of the study. In all groups of animals with an exposed papilla, Uosm was lower than in non-exposed animals. Outer cortical SNGFR in rats with exposed papillae, regardless of time, was not different from that in control rats. Inner cortical SNGFR after 45 and 90 min of exposure did not differ from that in controls, but after 15 min of exposure it was lower than in control animals. Outer and inner medullary plasma flow did not differ between rats with exposed papillae and controls, irrespective of exposure time. In conclusion, papillary exposure results in a permanent decrease in urine osmolality. This impairment of the concentrating ability cannot be attributed to prolonged changes in renal haemodynamics.     

Regulation of superficial nephron filtration rate by tubulo-glomerular feedback

Summary Possible regulation of glomerular filtration rate by tubulo-glomerular feedback from a late tubular site was studied in microperfusion experiments on rats. During perfusion of loops of Henle with varying flow rates and different perfusion solutions, filtration rate of the perfused nephrons was measured by total proximal fluid collection and inulin determination. During perfusion with isotonic Ringer's solution nephron filtration rate decreased significantly with increasing perfusion rates. Since proximal intratubular pressure was experimentally kept constant, this response must reflect decreased glomerular capillary pressure. Increasing the flow rate during perfusion with isotonic sodium sulfate or mannitol solutions was not associated with significant changes of filtration rate. Thus some correlate of the flow rate of normal loop of Henle fluid can affect filtrate formation. Such an effect may be mediated by the juxtaglomerular apparatus. Our results are consistent with the concept that the triggering signal is a function of the amount of distal sodium that is able to permeate the cell membrane at the receptor site rather than of distal intratubular sodium concentration.On leave from the Department of Physiology, University of Melbourne as recipient of a scholarship from the Deutscher Akademischer Austauschdienst.     

Developmental changes in nephron number, proximal tubular length and superficial nephron glomerular filtration rate of rats.

1. Post-natal development of single nephron glomerular filtration rate, superficial proximal tubular length, nephron number and kidney weight have been studied in Sprague Dawley and in Wistar rats. 2. Superficial tubular length is a non-linear function of body weight or age. There seems to be a rapid growth until animals weigh about 150 g in Wistar rats. In this strain, growth is slower thereafter. This difference is not as evident in Sprague Dawley rats. 3. Nephron numbers increase over the same period at which rapid tubular growth occurs. 4. Sprague Dawley rats have somewhat fewer, but longer, proximal tubules than do Wistar rats. 5. In all animals weighing more than 100 g, SNGFR is linearly related to weight. For younger, smaller Sprague Dawley rats, the same linearity holds over the age range studied--older than 20 days of age. In Wistar rats, SNGFR relative to weight is less in young animals. 6. By relating SNGFR to total kidney GFR, evidence is obtained that maturation of renal function also involves a greater increase in filtration by superficial than by juxtamedullary nephrons.     

Effective poxvirus removal by sterile filtration during manufacture of plasma derivatives

As a consequence of the September 2001 terrorist events, programs to protect against further such acts including potentially the use of biological warfare agents have been launched in the USA and elsewhere. As part of these initiatives, Vaccinia virus was procured for the pre-emptive vaccination of key personnel against smallpox as well as population-wide protection after an eventual exposure. The introduction of this live virus into a population at a relatively large scale represents a theoretical challenge for the safety of the blood supply, and potentially for plasma for fractionation. To strengthen further the demonstration of safety margins for plasma derived products against Vaccinia virus, the capacity of sterile filtration procedures to remove the virus was investigated. An infectivity assay for the Vaccinia virus strain which represents the majority of smallpox vaccine stocks available currently was used to investigate the potential removal of this virus by sterile filtration processes during the manufacture of plasma derivatives. Vaccinia virus behaves as predicted based on its size, i.e., an artificially added virus load is removed about 10,000-fold by the sterile filtration procedures tested. As the current investigation covered a range of different protein concentrations, filter materials and filters from different manufacturers, the results obtained are considered to be widely applicable. The current investigation supports further the high safety margins of plasma derivatives against any potential Vaccinia virus content of plasma for fractionation. As the large size is a general feature of Orthopox viruses, the results would also provide assurance against poxviruses identified more recently, for example, Monkeypox virus.