Net Ultrafiltration May Not Eliminate Backfiltration During Hemodialysis with Highly Permeable Membranes

Backfiltration of dialysis solution can occur during hemodialysis with highly permeable membranes. A method has recently been developed for determining backfiltration rates in vitro at low dialysate flow rates by measuring changes in the local dialysate concentration of a marker macromolecule via sampling ports added to the hemodialyzer housing. In the present study, the influence of net ultrafiltration on backfiltration rates was determined for five commercial dialyzers containing membranes with different water permeabilities. In vitro experiments were performed (n = 3) using freshly donated whole blood at blood flow rates of 200 and 340 ml/min and at a dialysate flow rate of 100 ml/min. At zero net ultrafiltration, backfiltration rates increased with increasing membrane water permeability and ranged from 0.9 to 6.9 ml/min. At a net ultrafiltration rate of 10 ml/min, backfiltration was eliminated for dialyzers containing membranes with water permeabilities of less than 30 ml/h/mm Hg but remained significant for dialyzers with higher membrane water permeabilities. Therefore, despite a significant net ultrafiltration rate, backfiltration may still occur during hemodialysis with highly permeable membranes.     

Ultrafiltration and Backfiltration during Hemodialysis

Abstract: Ultrafiltration is the pressure-driven process by which hemodialysis removes excess fluid from renal failure patients. Despite substantial improvements in hemodialysis technology, three significant problems related to ultrafiltration remain: ultrafiltration volume control, ultrafiltration rate control, and backfiltration. Ultrafiltration volume control is complicated by the effects of plasma protein adsorption, hematocrit, and coagulation parameters on membrane performance. Furthermore, previously developed equations relating the ultrafiltration rate and the transmembrane pressure are not applicable to high-flux dialyzers, high blood flow rates, and erythropoietin therapy. Regulation of the ultrafiltration rate to avoid hypotension, cramps and other intradialytic complications is complicated by inaccurate estimates of dry weight and patient-to-patient differences in vascular refilling rates. Continuous monitoring of circulating blood volume during hemodialysis may enable a better understanding of the role of blood volume in triggering intradialytic symptoms and allow determination of optimal ultrafiltration rate profiles for hemodialysis. Backfiltration can occur as a direct result of ultrafiltration control and results in transport of bacterial products from dialysate to blood. By examining these problems from an engineering perspective, the authors hope to clarify what can and cannot be prevented by understanding and manipulating the fluid dynamics of ultrafiltration.     

An in vivo analysis of reverse ultrafiltration during high-flux and high-efficiency dialysis.

We have developed an in vivo pressure monitoring system to study the phenomenon of reverse ultrafiltration of dialysate during high-flux and high-efficiency dialysis. Under the usual operating conditions of either type of dialysis, driving pressures existed for reverse ultrafiltration of dialysate into the venous end of the blood compartment. Whether or not reverse ultrafiltration could be abolished at higher ultrafiltration rates was dialyzer-dependent, being least with high-efficiency dialysis. In addition, the degree of reverse ultrafiltration was affected by patients hematocrit, dialyzer inlet and outlet oncotic pressures, and the rate and direction of dialysate flow.     

The simulation of continuous arteriovenous hemodialysis with a mathematical model

We have developed a mathematical model that predicts the performance of continuous arteriovenous hemodialysis. Given patient (plasma protein concentration, hematocrit, mean arterial pressure, central venous pressure) and circuit (flow resistance, membrane hydraulic permeability, dialyzer mass transfer coefficient, ultrafiltrate column height, dialysate flow rate) characteristics as inputs, predictions of hydraulic and oncotic pressure distribution, filtration rate, blood flow, total, diffusive, and convective urea clearances are provided. The model was tested by perfusing a circuit with bovine blood under conditions of pure ultrafiltration, zero net ultrafiltration and dialysis, or combined ultrafiltration and dialysis (countercurrent dialysate flow at rates of 10, 20, and 30 ml/min). In order to permit computation, membrane hydraulic permeability and flow resistances were measured. Dialyzer mass transfer coefficient for urea could not be measured directly and so was determined by fitting model predictions to measured urea clearances. For all conditions of operation, a urea mass transfer coefficient of 0.014 cm/min successfully simulated the data. Predictions of blood flow, filtrate generation rate, and circuit pressure distribution were accurate. At lower dialysate flow rates, urea clearance approximated the sum of dialysate flow and filtration rate. At higher dialysate flows, however, departure from this ideal blood-dialysate equilibrium was observed. Model predictions regarding the relative contributions of diffusion and convection to urea clearance were explored. Under conditions of nearly perfect equilibration of urea between blood and dialysate at the blood inlet, the model predicts that the diffusive clearance of urea will increase with increasing rate of filtration and may exceed the rate of dialysate inflow.     

Solute transport in continuous hemodialysis: a new treatment for acute renal failure

A pumpless dialysis technique which combines continuous convection and diffusion was studied in 15 critically ill acute renal failure patients. Fluid identical in composition and purity to that used in peritoneal dialysis was continuously circulated (single-pass) at 16.6 cc/min through the dialysis compartment of a 0.43 m2 flat plate PAN membrane dialyzer. Whole blood clearances for urea, creatinine and phosphate averaged 25.3 +/- 4.4 cc/min, 24.1 +/- 5.5 cc/min and 21.3 +/- 5.6 cc/min, respectively. Over the range of blood flows studied (50 to 190 cc/min) clearances of these solutes were independent of blood flow rate but rather were determined by both dialysate flow rate and ultrafiltration rate. In contrast net fluxes of calcium and sodium were correlated only with ultrafiltration rate. Bicarbonate loss was 0.52 +/- 0.11 mEq/min; K+ balance varied with dialysate K+; glucose uptake from dialysate was 107 +/- 24.0 mg/min. In fresh non-clotting dialyzers, mean ultrafiltration rate was 8.1 cc/min. At QBi of 70 to 190 cc/min, dialysate and blood solute equilibrate yielding a total clearance equal to the dialysate outflow, or 25 cc/min, that is, the sum of dialysate flow rate plus ultrafiltration rate. In comparison to currently used continuous arteriovenous hemofiltration (CAVH), the exceptionally-high solute clearances obtained with continuous hemodialysis constitute a significant improvement in continuous renal replacement therapy.     

Factors affecting hemodialysis and peritoneal dialysis efficiency

Hemodialysis and peritoneal dialysis are two blood purification techniques that use similar operating systems. The hemodialysis system is based on three components (blood, membrane, and dialysate). The peritoneal dialysis system is based on the same components that can, however, be less manipulated and adjusted. In hemodialysis the blood flow is the main determinant of small solute removal thanks to a prevalently diffusive mechanism. Convection is also used to transport larger solutes across the membrane, but this mechanism relies on the high permeability coefficient of the membrane and high transmembrane pressure leading to high ultrafiltration rates. The membrane can therefore influence the performance of the techniques as far as solute removal and ultrafiltration are concerned. Finally, diffusion is facilitated by an improved distribution of dialysate flow in the dialysate compartment. This can be achieved with a special dialysate pathway configuration based on space yarns or micronodulation of the fibers. In peritoneal dialysis, blood flow and membrane characteristics can be less manipulated or almost not at all. The only variables are dialysate volume, flow, dwell time, and composition. Thanks to modification in these aspects of the dialysate, peritoneal dialysis techniques with different clearances and ultrafiltration rates can be accomplished.     

Influence of convection on small molecule clearances in online hemodiafiltration

BACKGROUND: Dialysis efficacy is mostly influenced by dialyzer clearance. Urea clearance may be estimated in vitro by total ion clearance, which can be obtained by conductivity measurements. We have previously used this approach to assess in vitro clearances in a system mimicking predilutional and postdilutional online hemodiafiltration with a wide range of QD, QB, and ultrafiltration rates. Our current study elaborates on a formula that allows the prediction of the influence of ultrafiltration on small molecule clearances, and validates the mathematical approach both experimentally in vitro and clinically in vivo data. METHODS: Two conductivimeters in the dialysate side of an E-2008 Fresenius machine were used. HF80 and HF40 polysulfone dialyzers were used; reverse osmosis water and dialysate were used for blood and dialysate compartments, respectively. Study conditions included QB of 300 and 400 mL/min and QD of 500 and 590 mL/min, with a range of ultrafiltration rate from 0 to 400 mL/min in postdilutional hemodiafiltration and to 590 mL/min in predilutional hemodiafiltration. Urea clearances were determined in the in vivo studies, which included 0, 50, 100, and 150 mL/min ultrafiltration rates. RESULTS: The ultrafiltration rate and clearance were significantly correlated (R > 0.9, P < 0.001) and fitted a linear model (P < 0.001) in all of the experimental conditions. The following formula fitted the experimental points with an error <2% for both postdilutional and predilutional online diafiltration in vitro, respectively. K = K0 + [(QB - K0)/(QB)] x ultrafiltration rateK = K0 + [((QD x QB)/(QB + QD) - K0)/QD] x ultrafiltration rate where K is the clearance; K0 is the clearance with nil ultrafiltration rate; QD is the total dialysate produced (in commercial HDF, QD = QDi + Qinf). Since weight loss was maintained at 0, ultrafiltration rate = infusion flow. QB is the "blood" line flow. The formula was also verified in vivo in clinical postdilutional hemodiafiltration with a QB taking into account the cellular and water compartments. DISCUSSION: In vitro, by simply determining the clearance in conventional dialysis, the total clearance for any ultrafiltration rate may be estimated in both predilutional and postdilutional online diafiltration with an error of less than 2%. The same applies to in vivo postdilutional hemodiafiltration when the formula takes into account the cellular and water composition of blood.     

Factors affecting urea clearance during continuous hemodiafiltration in the canine model

Continuous hemofiltration (CH) for the treatment of hypervolemia and electrolyte abnormalities in critically ill patients with acute renal failure has been shown to be an effective mode of therapy. This technique offers several advantages over peritoneal dialysis or hemodialysis: it is technically less complex, provides efficient ultrafiltration, and produces fewer hemodynamic disturbances. Recently, continuous hemodiafiltration (CHD) using a flow of dialysate fluid into the ultrafiltration chamber has been reported to augment urea clearance. The purpose of this study was to determine the blood flow and dialysate flow characteristics for optimal clearance of urea and creatinine using this technique. Six mongrel dogs (mean weight, 8.0 +/- 1.1 kg) underwent bilateral nephrectomy to induce anuric renal failure. Postoperatively, the animals were fluid resuscitated and fed ad libitum. Twenty-four hours following nephrectomy, venovenous hemofiltration was instituted. Blood flow was regulated via a roller pump, while dialysate flow was regulated using an infusion controller. An Amicon-30S hemofilter was used in the circuit. Blood flow rates of 5, 10, 15, 20, 25, and 30 mL/kg/min were used. Hemodiafiltration using Dianeal 1.5% solution was used in each animal. Net fluid losses via ultrafiltration were replaced using lactated Ringer's solution. Three of six animals survived for the complete five-hour hemofiltration period. No marked disturbances in electrolyte serum concentrations, including hyperkalemia, were observed. BUN concentrations were reduced by 35% and creatinine by 26%. Variation of the dialysate flow rate did not influence clearance of either urea or creatinine. Instead, clearance appeared to be flow dependent, and it was markedly increased at flow rates greater than 15 mL/kg/min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acetate transfer across membranes of artificial kidneys in vitro.

To determine the rate of acetate transfer across hemodialysis membranes and to investigate the factors which influence acetate dialysance, we performed experiments with Dow-4, Gambro-13.5, and Travenol UF-II artificial kidneys using 14C-acetate. The rate of acetate dialysance was influenced strongly by the rate of fluid flow through the blood path, similar to the dialysance of other low-molecular-weight solutes. The ultrafiltration of fluid from the blood path to dialysate reduced the rate of transfer of acetate from dialysate to blood. The dialysance of acetate was significantly less than that of urea, despite their nearly identical molecular weights. This was not due to the direction of solute transfer. Experiments with a Kaufman-Leonard dialyzer demonstrated that the permeability of Cuprophane membranes to urea was greater than that to acetate was; this may be due to the charged nature of acetate.     

Hydrostatic Ultrafiltration During Hemodialysis Using Decreasing Sodium Dialysate

Twelve patients underwent hemodialysis using dialysate containing 130 mEq/L sodium, and, on a separate occasion, dialysis using a dialysate of constantly decreasing sodium concentration (from 150 to 133 mEq/L). Hydrostatic ultra-filtration during dialysis was performed at a constant rate (900 ml/hr) during both treatments, and was continued until a substantial drop in mean arterial pressure (-15%) or symptoms were observed. A double-blind comparison of the two treatment modalities was thus achieved.
At the end of ultrafiltration, significantly more fluid had been removed using decreasing sodium dialysate (2.9 ± 0.3 kg) than when using the low-sodium dialysate (1.9 ± 0.2 kg, P<0.001). Plasma sodium concentration at the end of ultra filtration using decreasing sodium dialysate was not significantly different from the predialysis level.
Hydrostatic ultrafiltration using a dialysate of decreasing sodium level may prove to be a useful means of removing excess fluid asymptomatically from dialysis patients.     

Effect of dialysate composition on intercompartmental fluid shift

Effect of dialysate composition on intercompartmental fluid shift and hemodynamics was studied in 12 patients during 1.5 or 2 hours of hemodialysis without net ultrafiltration, using high (H;Na 154 mmol/liter), normal (N;Na 140 mmol/liter) or low (L:Na 126 mmol/liter) concentration dialysate. H dialysate was associated with a small (0.9%) increase in blood volume, a larger increase in plasma volume and a decrease in erythrocyte volume. L dialysate resulted in a 2.3% decrease in blood volume, a larger decrease in plasma volume and an increase in erythrocyte volume. N dialysate gave results which were intermediately between the other two dialysis conditions. There was no difference in the post-dialysis mean arterial pressure between the groups, although heart rate increased more during H dialysis than during the other two conditions. Change in blood and erythrocyte volume correlated significantly with change in plasma Na concentration and osmolality, but not with change in plasma urea concentration. We conclude that dialysate composition affects the movement of water into and out of the plasma and erythrocytes in a manner that can be accounted for by altered plasma concentrations of osmotically active substances.     

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.     

Rapid Fluid Extraction with the Gambro Ultradiffuser®

Four patients were given fourteen treatments with the Gambro Ultradiffuser®. One hour of ultrafiltration without dialysate and with negative pressure on the dialysate side was followed by four hours of dialysis with negligible transmembrane pressure (TMP). Mean fluid removal was 2678 ml per ultrafiltration period and the mean ultrafiltration rate was 37 ml/min. During the dialysis period, TMP was about +30 mmHg giving an ultrafiltration rate of 4 ml/min. Pulse rate was unchanged. Hematocrit increased 3%, plasma protein increased 21% and plasma albumin increased 25%. Plasma values of potassium, sodium, urea, creatinine and osmolality were unchanged.
One patient experienced a reversible hearing loss during two ultrafiltration periods and two patients had severe, yet reversible, cardiac arrhythmias. One patient had hypertension during the ultrafiltration period. Rapid extraction of fluid up to 49 ml/min was possible. The mean mean arterial pressure was unchanged though it exhibited great variation and three patients developed side effects.     

Blood flow, ultrafiltration and solute transport rate in continuous arteriovenous haemodiafiltration: the AN-69 flat-plate haemofilter.

We measured blood flow, ultrafiltration rate and uraemic solute clearance at different dialysate flow rates during CAVHD using the AN-69 0.43 m2 flat plate haemofilter. As filter performance depends on clinical conditions and operational characteristics, data were analysed in terms of resistance to blood flow, membrane index of ultrafiltration, and diffusive mass transfer coefficients. An attempt was made to construct nomograms that may be used both to predict filter performance and to compare different haemofilters with each other.     

Effect of peritonitis on peritoneal transport characteristics: glucose solution versus polyglucose solution

BACKGROUND: Peritonitis is a common clinical problem and contributes to the high rate of technique failure in continuous ambulatory peritoneal dialysis treatment. The present study investigated the effect of peritonitis on peritoneal fluid and solute transport characteristics using glucose and polyglucose (icodextrin) solutions. METHODS: A four-hour dwell was performed in 32 Sprague-Dawley rats (8 rats in each group), with 131I albumin as an intraperitoneal volume marker. Peritonitis was induced by an intraperitoneal injection of 2 mL lipopolysaccharide (100 microg/mL phosphate-buffered saline) four hours before the dwell. Each rat was intraperitoneally infused with 25 mL of 3.86% glucose [glucose solution control group (Gcon) and glucose solution peritonitis group (Gpts)] or 7.5% icodextrin solution [icodextrin solution control group (Pgcon) and icodextrin peritonitis group (PGpts)]. RESULTS: Net ultrafiltration was significantly lower (by 44%) in the Gpts as compared with the Gcon group, but was significantly higher (by 138%) in the PGpts as compared with the PGcon group. The peritoneal fluid absorption rate, including the direct lymphatic absorption rate, was significantly increased (by 78%) in the Gpts group as compared with the Gcon group. However, the total fluid absorption did not differ between the PGpts and the PGcon groups. The dialysate osmolality decreased much faster in the Gpts group as compared with the Gcon group, resulting in significantly lower (by 9%) transcapillary ultrafiltration in the Gpts group. In contrast, the dialysate osmolality increased faster in the PGpts group as compared with the PGcon group, resulting in higher (by 40%) transcapillary ultrafiltration in the PGpts group. The in vitro increase in dialysate osmolality was also higher in the PGpts group as compared with the PGcon group. The solute diffusive transport rates were, in general, increased in the two peritonitis groups as compared with their respective control groups. CONCLUSIONS: Our results suggest the following: (1) Peritonitis results in decreased net ultrafiltration using glucose solution caused by (a) decreased transcapillary ultrafiltration and (b) increased peritoneal fluid absorption. (2) Ultrafiltration induced by the icodextrin solution appears to be related to the increase in dialysate osmolality (mainly because of the degradation of icodextrin). (3) Peritonitis results in increased degradation of icodextrin and a faster increase in dialysate osmolality and therefore better ultrafiltration, whereas the fluid absorption rate does not change. (4) Peritonitis results in increased peritoneal diffusive permeability.     

Vascular reactivity during haemodialysis and isolated ultrafiltration: thermal influences

BACKGROUND.: The present study was performed to assess the role of the extracorporealblood temperature in the disparate cardiovascular response betweenisolated ultrafiltration and combined ultrafiltration-haemodialysis. METHODS.: In twelve stable dialysis patients (21–77 years), bloodpressure and heart rate (Finapres) as well as forearm vascularresistance and venous tone (strain-gauge plethysmography) weremeasured during 1-h isolated ultrafiltration and 1-h combinedultrafiltration-haemodialysis (bicarbonate, sodium 141 mmol/l)at a fixed ultrafiltration rate of 0.91 l/h. The sequence ofboth treatment modalities was randomly defined within each patient.Serving as his or her own control, each patient was studiedat two different dialysate temperatures: 37.5 and 35.0°C. RESULTS.: At a dialysate temperature of 35.0°C extra-corporeal bloodcooling during combined ultrafiltration-haemodialysis was comparableto isolated ultrafiltration. The cardiovascular response inisolated ultrafiltration was characterized by a significantincrease in both forearm vascular resistance and venous tone,while heart rate even decreased. As a result, blood pressureremained unchanged or even increased. In contrast, during combinedultrafiltration-haemodialysis at a dialysate temperature of37.5°C the increase in forearm vascular resistance was onlysmall and insignificant, while venous tone decreased significantly.Heart rate tended to increase. Combined ultrafiltration-haemodialysisat a dialysate temperature of 35.0°C was also associatedwith a small increase in forearm vascular resistance. However,venous tone remained stable while heart rate decreased. At bothdialysate temperatures, blood pressure was well maintained. CONCLUSIONS.: We conclude that differences in cardiovascular reactivity betweenisolated ultrafiltration and combined ultrafiltration-haemodialysisare only partially explained by differences in the extracorporealblood temperature. In addition, especially venous reactivityis improved by lowering the dialysate temperature.     

The Allient dialysis system

The Allient is a dialysis system that combines various technologies to allow dialysis to be performed at sites outside of dialysis units (intensive care unit [ICU] or home) with ease and safety. A sorbent column regenerates dialysate, removing toxins and providing ultrapure dialysate from only 6 liters of tap water. The use of the sorbent column eliminates the need for costly and complex water purification systems. The Pulsar Blood Movement System provides blood flow at constant negative or positive pressure through single-lumen or dual-lumen accesses, maximizing blood flow rate while eliminating bothersome pressure alarms. Ultrasonic flow monitors control the operation of the pump and ensure adequate blood flow during each dialysis treatment. A completely disposable blood tubing and dialysate circuit eliminates the need for sterilization of the machine. The Allient should make dialysis in the ICU or home setting much more practical, reducing training requirements and increasing safety.     

Bicarbonate and calcium kinetics in postdilutional hemodiafiltration.

Hemodiafiltration (HDF) is a very effective blood treatment resulting from the coupling of dialysis and hemofiltration and leading to reduction of dialysis time. The aim of this study was to evaluate the balance of bicarbonate and calcium through the filter during postdilutional HDF (with an ultrafiltration flow rate of 70 ml/min) and to verify the effect of ultrafiltration on the kinetics of these two solutes. The study was performed by simultaneously collecting three blood samples (at filter inlet and outlet and after reinfusion) at different ultrafiltration flow rates (12.5-90 ml/min), to measure blood pH, pCO2, plasma total CO2(TCO2), total calcium, ionized calcium and plasma protein concentration. Plasma bicarbonate concentration was calculated by measuring plasma TCO2. The results showed an inverse linear relationship between bicarbonate (r: -0.7938; p less than 0.001) and calcium (r: -0.8731; p less than 0.001) balance and ultrafiltration flow rate. In particular, in postdilutional HDF both bicarbonate and calcium balances through the filter were negative at ultrafiltration flow rates greater than 40 and 55 ml/min, respectively. The negative bicarbonate balance, however, was corrected by reinfusing a substituting solution containing bicarbonate (40 mmol/l). By contrast, the negative calcium balance cannot be corrected by reinfusion and requires a greater calcium concentration in the dialysate and oral calcium supplements.     

The Accurate Control of Ultrafiltration

An apparatus has been constructed to regulate ultra-filtration accurately during dialysis. The principle of the apparatus is that, per unit of time, exactly the same amount of dialysate is introduced into the dialyzer as is discharged from it. The apparatus consists of two isovolumetric pumps connected in line. The four compartments of the two pumps must change their functions at every pump stroke. This is accomplished by a switching system. There is a continuously closed dialysate circuit. The fluid extracted from this circuit will be replenished from the blood compartment of the dialyzer. Ultrafiltration is regulated by a simple peristaltic pump, which sucks the fluid out of the closed dialysate circuit. The isovolumetric pumps and the switching system are driven by the elevated pressure of the dialysate (0.5–1.0 atm). The apparatus can be used in single pass dialysis. Dialysis in accordance with the Bergström principle can be simply performed.
In over 5,000 dialyses with several types of dialyzers, ultrafiltration was always accurate within the measuring limits. Considerable improvement was noticed in the well-being of the patients; hypotension, nausea, vomiting and muscle cramps were not seen.