Note: Descriptions are shown in the official language in which they were submitted.
112495Z
METHOD AND APPARATUS FOR CONTINUOUS, AMBULATORY PERITONEAL
DIALYSIS
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates generally to the field of Surgery,
and more particularly to fluid infusion methods and devices for
performing peritoneal dialysis within a patient.
2. Description of the Prior Art
Several of the functions performed by human kidneys
are the removal of waste metabolites, the maintenance of
fluid, electrolyte and acid-base balances, and hormone
and enzyme syntheses. The foregoing is discussed by
Abbrecht, P.H.,'bn Outline Renal Structure and Function",
CEP Symp. Series, 64, 1 ~1968). Abbrecht ~1968) forms
the first reference in the appended Bibliography which
appears after the disclosure and prior to the claims.
References from the Bibliography are referred to
throughout the specification by use of superscripts, for
example, Abbrecht (1968)1. Loss of normal kidney function
~acute or chronic renal insufficiency) is generally treated
~. '
llZ4~5Z -
through dialysis therapy or transplantation. Transpla~-
tation, if successful, restores all the normal functions.
Dialysi3 partially replaces some of the normal kidney
functions. For example, it does not replace the hormone
or enzyme functions, among others, as evidenced by the
greatly reduced blood hemoglobin levels in chronic uremic
patients.
Two types of dialysis thereapy are generally employed.
Bemodialysis is most commonly used in which the blood is
lo cleansed by passage through an artificial kidney in an
extracorporeal membrane system. The waste metabolites
diffuse across the membrane and are removed by a washing
dialysate solution. Excess fluid is removed by pressure-
induced ultrafiltration. The other approach is termed
peritoneal dialysis, in which the dialysate solution is
infused directiy into the abdominal cavity. This cavity
~B lined by the peritoneaL membrane which is highly vas-
cularized. r~etabolites ar~ removed by diffusion from the
blood to the dialysate acros ~le peritoneal membrane.
Excess fluid is removed by osmosis induced by a hyper-
tonic dialysate solution.
Current dialysis treatments are generally performed
interm~ttently under high efficiency conditions. The
treatments are usually performed two or three times per
week. The length of the treatment depends upon the de-
sired reduction in blood waste metabolite levels, but
u~ually averages 4-6 hours per hemodialysis and 24-48
hours for peritoneal dialysis. The time difference re-
flects the higher efficiency of hemodialysis, which is a
primary reason for its greater popularity. Both proced-
ures result in partial correction of abnormal metabolite,
fluid, electrolyte and pH levels during the treatment.
-- 2 --
1124~S~
Blood metabolite levels are greatly reduced followed by a
slow concentration buildup between dialyses. ~jellstrand
(1976) has hypothesized that the resulting concentration
fluctuations may be detrimental to the patient's health.
In fact, high efficiency hemodialyzers are not generally
u~ed to their full potential because of a characteristic
disorder termed the "disequilibrium syndrome" which devel-
Op8 in certain patients. These patients develop headache,nausea, vomiting, and severe blood pressure alterations
0 after two to three hours of dialysis. ThLs conditlon often
persists throughout the treatment leaving the patient weak
and exhausted. It is hypothesized by Arieff3 et al. (1975)
that this syndrome i9 a result of large in~racellular to
extracellular concentration ~and osmotic) gradients with
concomitant fluid shifts, particularly across the-~blood-
brain barrier".
Ihe Arieff hypothesis is supported by the results of
Popovich, et al. (1975) who have investigated the conse-
quences of physiological resistance on metabolite removal
from the patient-artificial kidney system. Vitamin B-12
~nd inulin were selected as representative middle mole-
cules in their investigation. They have shown that very
lit~le of the larger test metabolites are cleared from
the intracellular body pools during the dialysis treatment.
This is caused by the high resistance to mass transfer
across the cellular membranes and results in a large post
dialysis concentration rebounds as the pools equilibrate
ln the interdialytic period.
The conventional hemodialysis procedures use an
~nordinately large amount of dialysate fluid, approximately
450 liters/week. It is contemplated that the procedure
of the present invention will utilize approximately
70 liters/week.
- 3 -
1124~52
SUMMARY OF THE INVENTIO~
The Continuous Ambulatory Peritoneal Dialysis (CAPD~
process of the present invention differs in several funda-
mental ways from all current conven~ional dialysis processes.
It is totally different from the most popular process (hemo-
dialysis) in that it employs a natural body membrane which
obviates the need for an artificial kidney or for blood
acces~.
The fact that CAPD is continuous results in stable,
low blood toxic levels. Current peritoneal dialysis pro-
~esseS are intermittent (usually employed extensively two
or three times per week). Such intermittent treatment
result~ in wide toxin fluctuations at much higher levels
than CAPD, which is detrimental to the patient's well-~eing.
The CAPD process obtains optimum use (100% efficiency)
of dialysate fluid. Current processes employ short resi-
dence times with the intent of minimizing toxin levels in
the dialysate to achieve the maximum toxin removal rate.
- The~e inefficient high removal ratès are required because
of the short intermittent nature of current processes.
The CAPD process is ambulatory - the patient being
free to perform his normal daily duties while being treated.
Patients undergoing conventional peritoneal dialysis pro-
cesses are not ambulatory. They must remain by their di-
alysate supply (usually by machine) during the entire 24
to 48 hours of their treatment.
The CAPD process i~ economical to use - no machines
at all are required. The contemplated usage of dialysate
fluid is approximately 70 liters/week compared with
450 liters/week for conventional hemodialysis.
The greatest advantage of all is the overall comfort
and well-being of the patient using the CAPD.
_ . . ._. .
112495Z
The invention comprehends portable apparatus for carrying
out continuous, ambulatory peritoneal dialysis, which involves
establishing a substantially constant presence of dialysate
fluid within the peritoneum of a patient at all times over an
extended period of time. The apparatus includes an in-dwelling
catheter adapted to be surgically implanted in the peritoneal
cavity of a patient and having a supply tube for extending
through the abdominal wall of the patient, and a bag adapted to
be interconnected with the supply tube and carried by the patient
during dialysis for dispensing dialysate fluid through the supply
tube to the peritoneal cavity of the patient and for receiving
spent dialysate drained from the peritoneal cavity of the patient.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an exploded view of the components of the CAPD
system of the present invention;
FIG. 2 is a schematic view of the invention as intended
to be used on a patient;
FIG. 3 is an exploded perspective view of a wearable
microbiological filter unit designed for use as an auxiliary
component in the system; appearing with Fig. l; and
FIG. 4 is a fragmentary schematic view of an air bubble
trap and flow directing valve also adapted for use in the system.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIIIENT
The continuous, ambulatory peritoneal dialysis system of
the present invention is illustrated in simplest form in FIG. 1
and is designated generally by the numeral 10. The overall sys-
tem 10 comprises: an infusion system 11, a catheter system 12,
and a cap and drainage system 13.
The infusion system 11 comprises a dialysate bottle or bag
15 having an outlet tube 16 which terminates at one-half of a
quick connect coupling 17. An adjustable flow control clamp 18
is attached to the tube 16 for regulating the rate of fluid dis-
charge from the bag 15. The bag 15 preferably has a volume
capacity of 10 to 12 liters and has graduations at 2 liter inter-
vals. The bag 15 may also have a hook 19 at its top for hanging
it at some desired elevation above the attachment to a patient.
The catheter system 12 comprises a surgically implanted
in-dwelling catheter 20 having a connecting tube 21 which termi-
llZ4~5Z
ates at a matin~ half of a quick connect coupling 22, and aDacronTM cuff 23 which is surgically implanted in the abdominal
wall of a patient. The peritoneal catheter 20 may be, for
example, a Goldberg Balloon type as supplied b~7 the American
Medical Products Corporation, or a Tenckhoff catheter. The
catheter 20 is formed with a plurality of holes 24 and a flexible
rib cage 25 adapted to prevent occlusion of the holes 24 during
drainage. The DacronTM cuff 23 is adapted to allow tissue in-
growth and thereby provide an effective barrier to the entry of
bacteria into the peritoneal cavity. The tube 21 extends through
the Dacron cuff 23 and provides external connection by means of
the coupling 22.
The cap and drainage system 13 comprises an attachable cap
30 for mounting on the coupling 22 during the ambulatory residence
period, a disposable drainage tube 31, and a sterile drainage con-
tainer 32 for receiving used dialysate. The tube 31 carries a
mating half of a quick connect coupling 33 for attachment to the
coupling 22 during the drainage period.
In operation, the CAPD system 10 is utilized as follows:
Dialysate fluid is infused into a patient by attaching the
coupling 17 to the coupling 22 and allowing approximately 2
liters to pass through the tube 16 to the catheter 20. The rate
of flow of the fluid is controlled in a conventional manner by
adjustment of the flow control clamp 18. The coupling 17 is
then disconnected and the cap 30 placed on the coupling 22 for
the ambulatory residence period which may last for approximately
4 to 5 hours. The cap 30 is then removed and the drain coupling
33 attached to the coupling 22. The spent dialysis fluid is
drained from the patient's peritoneal cavity by gravity through
the tube 31 into the drainage container 32. The cycle just
described is thenrepeated so as to maintain a substantially
constant presence of the dialysate fluid within the patient and
thereby provide for continuous dialysis.
-- 6
, ~,,
11'~495Z
A ~lightly modified e~bod.iment of the invention is
illustrated in FIG. 2 which shows the CAPD system as in-
tended to be used on a patient. The system illustrated
includes a wearable millipore filter unit 40 intended to
minimize the introduction of bacteria into the peritoneal
cavity during infusion of dialysate fluid. The filter
unit 40 i5 interposed in the supply line 16 between the
supply bottle 15 and the indwelling catheter 20. The
filter unit 40 comprises a relatively flat filter body 41,
10 . a fluid inlet conduit ~2, and an outlet tube or conduit 43.
The lnlet tube 42 has a quick connect ~coupling 44 adapted
to be attached to the coupling 17. The outlet tube 43
i8 attached to one branch of a "T" connector 45. A second
branch of the "T" connector is att,ached to a tube 46
leading to the catheter ~0, and the third branch is con-
hected to a tube 47 which leads to the drainage bottle 32.
The tube 47 carries a quick connect coupling 48 adapted
to be attached to the coupling 33 of th~ drain tube 31.
Fluid cut-off clamps 49 and 50 are attached to the tubes
43 and 47, respectively. The clamps 49 and 50 are re-
lea~ed alternately during infusion and drainage,
respectively.
The wearable microbiological filter unit 40 is shown
ln exploded form in FIG. 3. The unit comprises the rela-
.
t~vely flat and flexible body or housing 41, a central
leaf-type filter 51, the inlet tube 42, and outlet tube 43.
The outer shell or housing 41 preferably is made of two
halves 54 and 55 cast from flexible, medical grade sili-
cone elastomer bonded together into a ~hape that can con-
form to body curvature. The halves 54 and 55 also may be
~formed with raised longitudinal spines 56 and 57, respec-
tively, adapted to prevent collapse of the outer shell
against the filter Si. The fllter 51 preferably is formed
- 7 -
4~.5~
of two sheet~ 58 and 59 of 0.22~ pore size membrane mater-
ial bonded together at their edges. The inlet tube 42 and
outlet tube ~3 preferably are made of standard, commercially
aYailable silicone elastomer. tubing.
It is deemed desirable, if not imperative, to minimize
~he risk of introducing air into the peritoneal cavity
during infusion of the dialysate fluid. To this end, a
device such as the bubble trap and flow directing val~e 60,
lllustrated schematically in FIG. 4, may also be included
0 to advantage wi~hin the system 10. The valve structure 60
shown can supplement or substitute for the "T" connector
45 and clamps 49 and 50. The valve 60 comprises a rela-
tively flat valve body 61, preferably made of clear plas-
tic, and a rotatable valve core 62, also preferably made
of clear plastic.~ The valve body 61 i9 formed with an
inlet channel 63, an ou~let channel 64, a drain channel
65, and an air bleed channel 66. The valve core 62 is
formed with interconnected radial channels 67, 68, 69,
and 70, as illustrated. The inlet channel 63 and outlet
channel 64 are constructed so as to form an inverted "U"
configuration. The inlet channel 63 is connected to the
outlet tube 43 of the filter unit 40. (Alternatively,
the entire valve structure 60 may be constructed as an
integral part of the filter unit 40). The outlet channel
64 is connected to the catheter 20, and the drain channel
65 is adapted to be connected to the drainage bottle 32.
With the valve structure 60 oriented in a vertical
plane, and with the valve core 62 turned to the "A" posi-
tion,~(as shown in FIG. 4A), any air trapped in the chan-
nels 63 and 64 can be bled through the air bleed channel66 to atmosphere.
Once all the air has been bled from the line, the
valve core 62 is turned to the "I" position (as shown in
- 8 -
1~4~5Z
FIG. 4B) for infusion of dialysate fluid through channels
63, 68, 67, and 64 to the catheter 20. ~en the desired
amount of fluid has been infused, the coupling 17-44 is
di~connected and a cap placed on the coupling 44 for the
period of residency. The coupling half 48 is also capped
during the residency period.
After the desired period of residency within the
peritoneal cavityj the spent dialysate fluid is drained
by uncapping the coupling half 48, connecting the coupling
33 to 48, and turning the valve core 62 to the "D" position
~as shown in FIG. 4C). In this position, the inlet channel
63 is cut off, and fluid is drained backwards through the
outlet channel 64, through channels 70 and 68 to the
drain channel 65. When drainage has been completed, the
valve core 62 is returned to the "I" position, the drain
bottle 32 disconnected, and the supply bottle 15 recon-
nected for infusion to the,inlet tube 42. The cycle is
then repeated as described above.
' It is contemplated that the filter unit 40 and valve
~tructure 60 may be flushed periodically with a formalin
solution, or the like, to prevent the growth of bacteria
within the filter and related conduits. To accomplish
this, the valve core 62 is turned to the "Fn~position (as
shown in FIG. 4D), and communication to the outlet channel
64 is cut off. The formalin solution is passed through
the inlet tube 42, filter unit 40, through inlet chan'nel
63j valve core channels 70 and 68 to the drain channel 65.
, m e formalin solution is cleared by passing through a
portion of dialysate fluid the,reafter, before turning the
valve core 62 to the "I" position for,infusion.
11~4~SZ
~THE~TICAL MODEL
The blood metahollte levels of patients are governed
by a balance between the generation rate and the removal
rate of the particular toxin ln question. Theoretical re-
lationships have been deri~ed which predict the predialysis
metabolite concentrations under discontinuous hemodialysis
and peritoneal dialysis situations5 7 Similar expressions
~ave been derived which predict the ln~tantaneous blood
~nd dialysate metabolite concentration levels during peri-
toneal dialysis infusions. These analyses result in
equations which are fairly complex for the general case.
If steady state conditions can be assumed, ~he equations
can be greatly simplified. Under these conditions, the
steady state blood metabolite level CB is given by:
.
- CB ~ ~
where G is the net generation rate and K is the total
~olute clearance (the sum of the dialysis clearance plus
the residual renal clearance).
Alternatively, the net solute clearance necessary to
maintain a prescribed blood metabolite level may also be
computed. For example, equation (1) predicts that a total
- clearance of 7.1 ml/min is required assuming that a steady
state blood urea nitrogen (BUN) concentration level of
70 mg/dl is desired with a BU~J generation rate of 5.0 mg/min
~15.4 g urea/day). This corresponds to a total clearance
. ..... , _ .
of approximately 10 liters per day.
Thls result is routinely employed by nephroiogists.
Patients are generally p~aced on some dialysis regimen
when their residual renal clearance diminishes signifi-
cantly below 7 ml/min.
-- 10 --
l~Z4~5Z
The mathemati~al model also presents a simplification
whlch i~ possible if the dialysate fluid totally equili-
brates with the blood, i.e., CD = C~. For these conditions,
the dialysance clearance equals the dialysate flow rate,
QD, and equation (1) can be rewritten as:
G
2)
~here KR = residual renal clearance. For the anuric case
(RR ' 0), and equation (2) further simpli~ies to:
.
CB D G (3)
QD
This analysis yields the hypothesis that a patient
c~n be adèquately dialyzed with acceptable B~l levels if
only 10 liters of dialysate fluid per day are allowed to
continuously equilibrate with body fluids (i.e. a dialysis
clearance of 7.0 ml/min and a steady state BUN level of
approximately 70 mg/dl).
CLINIC~L TECHNIQUE . ~
The desired equilibration of meta~olite between blood
~nd dialysate fluid can be readily accomplished with inter-
mlttent peritoneal dialysis utilizing the system 10 descri-
bed above. Normal peritoneal dialysis procedure is to
infuse 2 liters of dialysate with a re~idence time of lS
to 60 minutes. I have discovered that if the residence
time 1s extended to approximately 4~ hours, a patient can
perform 5 exchanges per day with sufficient time for in-
fusion and drainage. Thi~ long residence period has been
found to be sufficient for equilibration between plasmn
and the dialysate for urea and creatinine. Five exchanges
per day at two liters per exchange yields the 10 liters/day
which has been hypothesized to be required to maintain the
' ~ llZ4,95Z
patient with acceptable B~N levels. Steady state may be
a~sumed since five exchanges are performed each day with
relatively long residence times which compares favorably
wlth the usuàl three hemodialysis trea~ments per week.
Thig equilibrium peritoneal dialysis technique is funda-
mental to the Continuous, Ambulatory Peritoneal Dialysis
procedure of the invention de~cribed and claimed herein.
.
' EXAMPLE
Equilibrium peritoneal dialyQis according to the
present invention was aonducted on a 40-year old, 190 lb.,
5 ~ 9 n male over a five-month period through use of an in-
dwelling Tenc~hoff catheter. The patient had a history
of surgical removal of his right kidney at an early age
s~condary to a traumatic injury. He had developed neph-
rotic syndromé approximately 18 months prior to reaching
end stage renal disease. He had well established athero-
~clerotic coronary artery disease with angina pectoris.
Caxdiac catheterization and coronary arteriography revealed
atherosclerotic changes of the left circumflex coronary
~rtery and a 90% occlusion of small obtuse marginal branch
on that side. The right coronary artery revealed stenosis
1 cm. long in the mid portion with approximately 50% ob-
struction. ~e was said to have had Buerger's disease at
~ge 28 and had previously had a surgical procedure on the
,left iliac area at that age. A gastric mucosal biop~y
demonstrated Menetrier's disease at age 39. ~e had hyper-
cholestolemia and hypertriglyceridemia ~nd had been diag-
nosed as having mild adult onset diabetes for approximately
four years. Both his father and mother had diabetes, the
mother requiring insulin. ~is glomerular filtration rate
in September, 1974, was 14 ml/min, with a creatinine level
- 12 -
~ 124~5~
of 9.9 mg/dl. He had 8 gram~ of protein ln the urine per
24 hours at that time.
On eight separate occasions, efforts were made to
establish a subcutaneous arteriovenous fistula, or the
establishment of a Quintin-Schribner shunt. All of these
~ttempts were unsuccessful because of thrombosis; only on
one occasion was a fistual utiiized for a ~ingle dialysis.
It wa~ recommended to the patient that he be transferred
to a center where chronic peritoneal dialysis could be
lnstituted. This the patient was unwilling or unable to
do. In view of these circumstances, the equilibrium-
peritoneal dialysis technique defined herein was undertaken
~8 a llfe-saving necessity.
After obtaining appropriate ~nformed consent, the
procedure of peritoneal dialysis using S two-liter exchanges
per 24 hours was instituted. Infusion required 10 minutes,
relying only on hydrostatic pressure, and was followed by
nn equilibration period averaging 260 minutes. Drainage
o~ the dialysate averaged fifteen minutes. Three minutes
wer¢ required for tubing connection yielding 288 minutes
per exchange. The procedure was originally conducted with
Dianeal~ 1.5% solution in the hospital. This did not
allow for adequate water removal, so 4.25% solution was
substituted on a variable schedule until it was determined
that alternate 1.5% and 4.25~ solutions could be used to
remove approximately 2000 cc. of fluid per day in excess
of that instilled into the peritoneum; the patient was un-
cooperative in maintaining fluid restrictions. The pro-
oe dure was carried out on an experimental basis by the
patient in the hospital for approximately one month. After
~tabilization of the patient on the new procedure, he was
trained to conduct the procedure in his home. Within the
first month at home ne had an episode of peritonitis which
- 13 -
~ 1~24~952
subsequently resulted in obstruction of the chronic peri-
' toneal catheter. The catheter was replaced and, subsequentto that, no obstructive problems developed.
The patient complained of intermittent abdominal pain
whlch was felt to be related to the 4.25~ hypertonic solu-
tion or to the pH of the solutions. The pH was adjusted
w~th sodium bicarbonate, but he continued to exhibit inter-
mittent abdominal pain. This did ~o't, however, prevent
him from carrying out normal physical activity, including
10, making several trips to distant cities by carrying his
dia,lysate solutions with him in the back of his car.
The patient also complained of intermittent difficulty
ln sleeping because of abdominal distension.
The patient was oliguric during the course of the
study. He had an estimated creatinine residual renal
clearance of'5.0 ml/min and was anorexic with nausea and
vomiting at the ihitiation of the study on June 30, 1975.
His B~1 was '70 mg/dl while under strict dietary protein
restriction. Immediately after commencçment of treatment
in the hospital his diet restrictions were removed and
his B~l's remained at 70 mg/dl with a significant increase
in patient well-being. The BUN levels then diminished and
stahilized in the 35 to 45 mg/dl range with creatinines
in the 7,to 10 mg/dl range. The alleviation of the symtom~
of chronic uremia in the patient was comparable to parients
on hemodialysis. A creatinine residu~l clearance of 3.0
ml/min was measured on 10/20j75. The treatment was contin-
ued by the patient in his homè until 12/9/75 at which time
he was successfully transplanted with a cadaveric C-match
kidney. ~le currently has a glomerular filtration rate of
96 ml/min.
'
- 14 -
llZ4~5Z
CLINIC~L BV~LU~TION
Clinical evaluation of the above example has been
conducted and rcported in the technical literature8 In
order to quantify the treatmcnt, the concentr~tion levels
of urea, creatinine, uric acid, glucose and tritium tagged
cyancobalamin were follo-~ed on a single exchange on ll/14/75
and on a multi-day basis. The single exchange study was
conducted by inj~cting a loading dose of lOOOyg of cyan-
ocobalamin followed 24 hours later by the tagged cyanco-
balamin. ~fter an additional 24-hour equilibration period,
blood and dialysate sam~les were obtained at 30-mlnute
intervals throughout the equilibration period.
Representative dialysate samples were ohtained by
m~ing _ situ via withdrawing and reinfusing, 50 ml of
dialysate ten times immediately prior to aspiration of
~he sample. Concentration levels of the uremic toxins
~ere det~rmined by use of the TechnicoTMsr~-l2 analyzer,
~hile cyanocobalamin levels were obtained via normal
~lquid scintillation counting tcchniqucs.
The dialysis clearances (KD) of the various substances
are normally determined from the average ~lood concentra-
tlon (CB), residence time (t), drained dialysate volume (VD)
and concentration (CD) by the expression:
CDVD ' ' '
~ ~ C t t4)
For the case of urea and creatinine, the blood and dialy-
~ate concentrations equilibrate, CD ~ CB~ such that the
equation (4) simplifies to:
RD ~ Dt s QD . ~5)
where VD is the drained dialysate volume (the sum of the
lnfusion volumc plus ultrafiltration volume).
5~ 5 -
llZ~5Z
The xesults for an average residence time of 288
~lnutcs are prcsented in Table I ~elow. The mean drained
dialysate volume for the patient was 2,400 ml.
TABL~ I -
uilibriu~ Peritoneal Dialysis Met _olite Clearances
Compound Mol. ~t. R, ml/min
Urea 60 8.3
Creatinine 113 8.3
Uric ~cid 168 7.7
lQ Cyanocobalamin 1355 5.7
.
The experimental ~ean urea dialysi~ clearance of
8.3 ml~min is slightly greater than the required clearance
value predicted in the development of the hypothesis. The
increase is caused by the ultra filtered fluid.
The residual creatinine renal clearance was determined
to be 3.0 ml/min three weeks prior to the quantative study.
From ~lis the total clearance, R, for urea and creatinine
can be estimated to be:
X ~ RD ~ R ~6)
R 8.3 + 3.0
~ ~ ; 11.3 ml/min.
Equation (1) above can be employed to calculate predicted
steady state concentration~ of urea and creatinine from
this value and the generation rate, G. The results plus
the experimental values are presented in Table ~I.
T-ABLE II
Predicted and ~xperimental Meta~olite Levels
Solute G,mg/min X,ml/min C ,predic- C~,experi-
~ed,ma~mental,~%
. .
Urea 5.0 11.3 44 35-45
Creatinine 1.4 11.3 12 7-10
- 16 -
52
Th~ predicted values are in good agreement with the
experimental results. It appears that t~e actual genera-
tion rates for the patient w~s less than those assumed for
the general patient population. This is in line with the
diabetic diet of the patient and the restricted activity
; resulting from his cardiovascular complications.
Middle molecule clearances as defined by Vitamin B-12
with this procedure are at acceptable levels. In fact, the
steady state middle molecule metabolite concentration-levels
of patients with this technique will be considerably less
than those undergoiny hemodialysis. For example, 18 hours~
week of hemodialysis at a B-12 clearance of 25 ml/min yields
a total clearance-tlme product o 27 liters/week. The cor-
responding equilibrium peritoneal dialysis clearance of
5,7 ml/min ~neglecting residual renal clearance) for
168 hours/week yields a total clearance-time product of
57 liters/week. This predicts that the middle molecule
concentration level for patients utilizing the new pro-
c~dure will be less than one-half of that of patients on
hemodialysis. This primarily caused by the increased time
factor, i.e., equilibri~m peritoneal dialysis is conducted
24 hours/day. The steady state character of the treatment
will also allow for continuous equilibration across the
cellular membrane which will circumvent the limitations
lmposed by inner body resistances which have been reported
for discontinuous hemodialysis techniques4
In summary, the CAPD system of the present invention
offers a number of significant advantages over existing
dialysis techniques. The fact that toxic solutes are re-
~oved continuously eliminates the di~comfort associated
with body adjustment to the wide fluctuation in chemical
imbalances that-occur before and after conventional dialysis.
.
- 17 -
! 1124952
The cArD process results in lo-~ blood toxic metabolite
levels ~hich can be prescribcd within limits by an attend-
lng physician by adjusting the dialysate volume infused.
The CA~D proces~ results in lo~er blood levels of
larger toxic solutes (so-called "middle molecules") because
Of lts contlnuous nature.
The CAPD process does not require blood acce~s as with
all conventional hemodialysis processes which constitute
approximately 90~ of current dialysis practice. The admin-
lstration of an anticoagulant (heparin) is not required.
There is no blood loss in equipment, or contact of blood
on foreigll surfaces as is true with all hemodialysis
processes.
The c~rD system does not require an artificial kidney
or the use of complicated equipment which must be.purchased
and maintained.
The CA~D system is wearable and the patient is free
to go about his normal activities while the dialysis is
being performcd.
The embodiments of the invention shown and described
are by way of example only, and it i9 to be understood that
many changes and modifications might be made thereto with-
out departing from the spirit of the invention.~ The inven-
tion ~s not to be construed as limited to the embodiments
shown and described, except in-so-far as the claims may
be so limited.
BIBLIOGRAPHY
1 Abbrecht P.H., "An Outline Renal Structure and Function",
CEP Symp. Series, 64, 1 (19683.
2 Kjellstrand, C.M., "Future Directions for the Ak-CUP
Program", Proceedings Contractors Conference, Artificial
Kidney Chronic Uremia Program, NIH, HEW 9, (1976).
3 Arieff, A.I., Guisado, R., Massry, S.G., "Uremic
-~ - 18 -
4~52
Encephalopathy: Studies on Biochemical Alterations in the
Brain", Kidney Intern., 7, S-194 (1975).
4 Popovich, R.P., Hlavinka, D.J.,Bomar, J.B., Moncrief, J.W.,
and Dechers, J.F., "The Consequences of Physiological
Resistances on Metabolite Removal from the Patient-
Artificial Kidney System", Trans. Amer. Soc. Artif. Int.
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Popovich, R.P., Moncrief, J.W., "The Prediction of
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