Artificial Organs

Artificial Organs: Thoughts & Progress

Vol. 3, No. 2

It is the goal of this section to publish material which provides information regarding specific issues, aspects of artificial organs’ application, approach, philosophy, suggestions and/or thoughts for the future.

Orally Diluting Hemofiltration

Tetsuzo Agishi, Norimase Yamashita, Yasuo Ozaku, Kazuo Era and Kazuo Ota f rom the Kidney Center, Tokyo Women’s Medical College, Tokyo, Japan.

Abstract Orally diluting hemofiltration (ODHF), herein re- ported, is a new technique where the body fluid is purified by cooperative procedures of dilution-sup- plementation with oral electrolyte solution and fil- tration using the RP-6 dialyzer. -One uremic patient was maintained for two months on a five-hour, three-times-per-week ODHF schedule, and another patient was maintained for four months on the same regimen with no supportive hemodialysis.

Introduct ion Many clinical experiences have shown tha t

uremic patients can be sustained in a reasonable condition on hemofiltration.1*2 Currently, the most critical problem in hemofiltration techniques lies in the supply of expensive solution which must be sterile and pyrogen-free since it is infused directly into the bloodstream to dilute the body fluid and supplement its loss by filtration.

It has been presumed, however, that the body fluid was replaced not only through a vascular route, but also through the oral route for the pur- pose of dilution and supplementation. For the latter case, the replacement fluid was not necessarily aseptic and pyrogen-free.

A study was conducted to investigate whether the electrolyte solution, orally administered in a re- latively short period of time, transferred into the intravascular compartment and maintained bal- ance when body fluid was lost by filtration. The ulti- mate goal was to ascertain the feasibility of main- taining homeostasis of the uremic patient using orally diluting hemofiltration.

Clinical Application After preliminary animal experiments, clinical

application was conducted in two uremic patients who had been on regular hemodialysis with creati- nine clearances of 0 ml/min and 4.9 mllmin, re- spectively, and urinary production of 0 ml/day and 600 ml/day, respectively. Both patients did not restrict water intake and often gained over 5 kg of their body weight between hemodialyses. These pa- tients were asked to drink about three liters of half- diluted Ringer’s lactate solution for five hours, while eight to nine liters of body fluid was removed by hemofiltration using an RP-6 dialyzer (Rhi3ne- Poulenc, Paris, France). ODHF was performed three times per week and continued for two and four months, respectively, without hemodialysis.

Prefiltration plasma concentrations of blood urea nitrogen and creatinine initially increased and reached a plateau at approximately 100 mg/dl and 13 mg/dl, respectively, within two to three weeks after the beginning of ODHF, while total protein concentration did not exhibit any marked change.

The plasma sodium level began decreasing gradually, but was normalized after salt intake was unrestricted; furthermore, about 40 ml of a 10% saline solution was infused during the procedure. Hyperkalemia developed, but was ameliorated after correction of acidosis as mentioned below. Muscular twitching occurred around two weeks after the be- ginning of hemofiltration, but disappeared with a n infusion of 40 mEq calcium. Plasma pH gradually shifted to acidotic and normalized after oral admin- istration of 5-10 gm/day sodium bicarbonate. There were no noticeable changes in hematology.

Discussion The observed clinical course was more satisfac-

tory than anticipated, and no dialysis was needed to maintain patients’ well-being even though electro- lytes had to be administered.

Surprisingly, less than 30 L/week of electrolyte solution for dilution-supplementation could sustain the well-being of these patients. On ODHF, the pa- tients’ creatinine clearances were 0 ml/min and be- tween 5.0-7.0 ml/min, respectively; urinary outputs were 0 ml/day and between 1,000-2,000 ml/day. The

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May, 1979 Thoughts and Progress

amount of fluid is much less than that previously used by Henderson’ and Quellhorst.2 The difference is assumed to be due to the difference in dilution modality.

ODHF is considered to point in a new direction of hemofiltration research since the necessary equipment is so simple. Based upon the principle of ODHF, a compact, wearable system has been de~eloped .~

References 1. HENDERSON, L. W., SILVERSTEIN, M. E., FORD, C. A,, LY-

SAGHT, M. J. Clinical response to maintenance hemofiltra- tion. Kidney Int, 7(1):S58, 1975.

2. QUELLHORST, E., DOHT, B., SCHUENEMAN, B. Hemofiltra- tion: treatment of renal failure by ultrafiltration and substi- tution. J Dial, 1:529, 1977.

3. OZAKU, Y., AGISHI, T., YAMASHITA, Y., ERA, K., OTA, K., ABE, M. , ONO, T. Non-dialysis type wearable artificial kidney system. JJMI, 48(4):182, 1978.

The Old and the New in Ultrafiltration Techniques

Todd S. Ing, Wei-Tzuoh Chen, John T. Daugirdas, W. Peter Geis” and Jessie E. Hano” from the Depart- ments of Medicine and Surgery, Veterans Adminis- tration Medical Center, Hines, Illinois, U.S.A., and “Loyola University Stri tch School o f Medicine, Maywood, Illinois, U.S.A.

Introduct ion During the past 50 years, great strides have been made in the development of various ultrafiltration techniques-39 In the course of rapid proliferation of ideas in this field, however, investigators have sometimes used different terms to designate one particular technique, or else have applied the same name to entirely separate procedures. As a result, considerable confusion has developed in the nomen- clature of ultrafiltration methods.26 With this in mind, we propose to review the terminology of these techniques, mindful of their recent evolution and current clinical application.

Ultrafiltration Techniques Ultrafiltration can be defined as the process

whereby a solution is passed under pressure through a filter or semipermeable membrane. The dispersion medium (solvent) and solutes up to a crit- ical particle size (depending upon the porosity of the

filter or membrane used) are transported through the filter by a process termed convection. The rate of ultrafiltration depends directly upon the hydro- static and osmotic pressure gradients in existence across the filtering membrane, and all solutes below a critical size “seive” through the membrane at the same rate. Convective transport is, thus, clearly dis- tinguished from diffusion, in which the rate of transport of a diffusible solute is a function of its molecular weight.

1. Dialytic u l t ra f i l t ra t ion During routine hemodialysis, both diffusion

and ultrafiltration occur simultaneously across the dialyzer membrane. Ultrafiltration toward the di- alysate compartment is driven by the naturally oc- curring hydrostatic pressure on the blood side of the membrane. A lesser osmotic pressure gradient in the opposite direction, i.e., towards the blood, is also pre- sent, because the osmolality of uremic plasma is or- dinarily greater than that of standard dialysate. The net result of these two forces is a modest amount of ultrafiltration towards the dialysate.

The distinction between “conventional dialy- sis” and “dialytic ultrafiltration”, then, becomes a matter of emphasis. We believe that the term dialy- tic ultrafiltration should be applied when the normal hydrostatic and osmotic pressure gradients of hemodialysis a r e modified to substant ia l ly increase the net amount of ultrafiltration. Thus, dialytic ultrafiltration can be performed by increas- ing the positive pressure on the blood side, or by creating a negative pressure on the dialysate side, of the dialyzer membrane.4,9,11 Alternatively, glucose, sodium or other osmotically active agents can be added to the dialysate to generate a n osmotic pressure gradient i n favor of the d ia ly~ate .~ ,”

Dialytic ultrafi l tration, as conventionally performed by increasing the hydrostatic pressure gradient across the dialyzer membrane, has cer- tain drawbacks. Patients often experience muscle cramps during the procedure, and may become hy- potensive even before substantial volumes of fluid have been removed.40 It has been speculated that the drop in plasma osmolality which takes place during dialysis may be responsible for these inap- propriate vascular reflexes.22 In support of this hy- pothesis, it has been shown that larger quantities of ultrafiltrate can be extracted from patients with fewer untoward effects when the concomitant dialy- sis is performed in such a way that the decrease in plasma osmolality is minimized. I t remains to be de- termined whether such new methods of dialytic ul- trafiltration, accomplished by adding sodium’ or urea35 to the dialysate, will be clinically useful.

Address for correspondence: Dr. T. S. Ing, Veterans Administration Medi- cal Center, Hines, Illinois, 60141, U.S.A.

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