Peritoneal Dialysis Equipment


Therapy Format

Fluid and Solute Removal

The Peritoneal Membrane: Physiology and

Transport Properties

Transport Modeling

Emerging Developments

Peritoneal Dialysis Equipment

Michael J. Lysaght

Brown University

John Moran

Vasca, Inc.

 

Irreversible end-stage kidney disease occurs with an annual frequency of about 1 in 5000 to 10,000 in general population, and this rate is increasing. Until the 1960s, such disease was universally fatal. In the last four decades various interventions have been developed and implemented for preserving life after loss of all or most of a patient’s own kidney function. Continuous ambulatory peritoneal dialysis (CAPD), the newest and most rapidly growing of renal replacement therapies, is one such process in which metabolic waste products, electrolytes, and water are removed through the peritoneum, an intricate membranelike tissue that lines the abdominal cavity and covers the liver, intestine, and other internal organs. This review begins with a brief summary of the development of CAPD and its role in the treatment of contemporary renal failure. The therapy format and its capacity for solute removal are then described in detail. Bioengineering studies of peritoneal transport, in which the peritoneum is described in terms analogous to the mass transfer properties of a planar membrane separating well-mixed pools of blood and dialysate, are then reviewed. The transport properties of the equivalent peritoneal membrane are summa­rized and compared to those of hemodialysis membranes. Models to describe and predict fluid and solute removal rates are examined. Finally, current developments and emerging trends are summarized.

The early history of peritoneal dialysis, as reviewed by Boen [1985], is contemporaneous with that of hemodialysis (HD). Small-animal experiments were reported in the 1920s and 1930s in the United States and Germany. Earliest clinical trials in acute reversible cases of kidney failure began in the late 1930s in the form of a continuous “lavage” in which dialysate was continuously infused and withdrawn from dual trochar access sites. Acute treatments were continued through the 1940s, and about 100 case reports appeared in the literature by 1950; sequential inflow, dwell, and withdrawal was increasingly favored over continuous flow. Chronic therapy was introduced in the early 1960s, followed shortly by indwelling peritoneal catheters. From 1960 onward, peritoneal dialysis clearly lagged behind HD, as the latter became more streamlined, efficient, and cost-effective. Although endorsed by a small group of enthusiasts and proponents, peritoneal dialysis had evolved into a specialized or niche therapy. This changed dramatically in 1976 when Popovich, a biomedical engineer, and Moncrief, a clinical nephrologist, announced the development of a new form of peritoneal dialysis in which ambulatory patients were continuously treated by two liters of dialysis dwelling in the peritoneal cavity and exchanged four times daily [Popovich et al., 1976]. Two years later Baxter began to offer CAPD fluid in flexible plastic containers, along with necessary ancillary equipment and supplies. The rapid subsequent growth of the process is tabulated in Fig. 131.1.

100000

Peritoneal Dialysis Equipment

1978 1982 1986 1990

FIGURE 131.1 The growth of peritoneal dialysis. Line and points refer to the total estimated worldwide peritoneal dialysis population; the numbers adjacent to the points are PD patients as a percent of total dialysis population. At the end of 1993, 14,000 of the 90,000 peritoneal dialysis patients utilized some version of APD; the remainder were treated with CAPD. Data compiled taken from various patient registries and industrial sources.

At this writing, approximately 90,000 patients are treated by CAPD (versus 490,000 by HD and 130,000 with kidney transplants). A more recent development is the introduction of automated peritoneal dialysis (APD), in which all fluid exchanges are performed by a simple pump console, usually while the patient sleeps. About one peritoneal dialysis patient in six now receives some form of APD; this approach is discussed more fully in a later section on emerging developments.

Both CAPD and HD have advantages and disadvantages, and neither therapy is likely to prove better for all the patients all the time. The principal attraction of CAPD is that it frees the patient from the pervasive life-style invasions associated with thrice weekly in-center HD. CAPD is particularly popular with patients living in rural areas distant from a hemodialysis treatment center. The continuous nature of CAPD eliminates fluctuations in the concentrations of uremic metabolites and avoids the sawtooth pattern of hemodialysis peak toxin concentrations. Fluid and dietary constraints are less restrictive for patients on CAPD than those on HD. A major complication of CAPD is peritonitis. Th rate of peritonitis was initially around 2 episodes per patient year; this has fallen to fewer than 0.5 episodes per patient year due to advances in administration set design and use. The morbidity of peritonitis has also decreased with increased experience in its treatment. In most cases, detected early and treated promptly, peritonitis can be managed without requiring hospitalization. Peritonitis caused by certain organisms including Staphylococcus aureus, Pseudomonas, and fungi remains a clinical problem. Other drawbacks of CAPD include the daily transperitoneal administration of 100-150 g of glucose providing D600 calories, and the tedium of the exchanges. APD and new solution formulations are being developed to address both issues. Little doubt now exists that risk-adjusted survival and morbidity for patients treated by CAPD is equivalent to that for patients treated with HD. On balance, the therapy seems well suited to many patients, and it continues to grow more rapidly than alternative treatment modalities.

Therapy Format

The process of CAPD is technically simple. Approximately 2 L of a sterile, nonpyrogenic, and hypertonic solution of glucose and electrolyte are instilled via gravity flow into the peritoneal cavity through an indwelling
Catheter 4 times per day. A single exchange is illustrated in Fig. 131.2. I Ntraperitoneal fluid partially equili­brates with solutes in the plasma, and plasma water is ultrafiltered due to osmotic gradients. After 4-5 hours, except at night where the exchange is lengthened to 9-11 hours to accommodate sleep, the peritoneal fluid is drained and the process repeated. Patients perform the exchanges themselves in 20-30 minutes, at home or in the work environment after a training cycle which lasts only 1-2 weeks. In APD, 10-15 L are automatically exchanged overnight; 2 L remain in the peritoneal cav­ity during the day for a “long dwell” exchange.

FIGURE 131.2 Illustration of the three steps involved in a single CAPD exchange: fluid infusion, dwell, and drain. Some administration sets require the bag to stay connected during dwell (it is rolled and fits in a girdle around the waist); others allow it to be disconnected. Drain and infusion take about 10 minutes each; three daytime dwells are 4-6 hours each; the overnight dwell lasts 8-10 hours.

подпись: 
figure 131.2 illustration of the three steps involved in a single capd exchange: fluid infusion, dwell, and drain. some administration sets require the bag to stay connected during dwell (it is rolled and fits in a girdle around the waist); others allow it to be disconnected. drain and infusion take about 10 minutes each; three daytime dwells are 4-6 hours each; the overnight dwell lasts 8-10 hours.
As will be discussed in more detail below, the drained fluid contains solute at concentrations around 90-100% of plasma for urea, 65-70% for creatinine, and 15-25% for inulin and D2 microglobulin. Net fluid removal ranges up to 1000 ml per exchange. CAPD generally removes the same quantity of toxins and fluid as HD ( a little thought will show that this is a require­ment of steady state, provided that generation is unal­tered between the two treatment formats); however,

CAPD requires a higher plasma concentration as the driving force for this removal. Steady-state concentra­tions during CAPD are typically close to the peak, i. e., pretreatment, concentrations of small solutes during HD but much lower than the corresponding peaks for larger species.

Access to the peritoneum is usually via a double-cuff Tenchkhoff catheter, essentially a 50-100 cm length of silicone tubing with side holes at the internal end, a Dacron mesh flange at the skin line, and connector fittings at the end of the exposed end. Several variations have evolved, but little hard evidence supports the selection of one design format over another [Dratwa et al., 1986]. Most are implanted in a routine surgical procedure requiring about 1 hour and are allowed to heal for 1-2 weeks prior to routine clinical use. Sterile and nonpyrogenic fluid is supplied in 2-L containers fabricated from dioctyl phthalate plasti­cized polyvinyl chloride. The formulation is essentially potassium-free lactated Ringers to which has been added from 15-42.5 g/L of glucose (dextrose monohydrate). The solution is buffered to a pH of 5.1-5.5, since the glucose would caramelize during autoclaving at higher pH levels. Several different exchange protocols are in use. In the original design, the patient simply rolls up the empty bag after instillation and then drains into the same bag following exchange. The bag filled with drain fluid is disconnected and a fresh bag is reconnected. Patients are trained to use aseptic technique to perform the connect and discon­nect. Many ingenious aids were developed to assist in minimizing breaches of sterility including enclosed ultraviolet-sterilized chambers and heat splicers. More recent approaches, known as the “O” set and “Y” set or more generically as “flush before fill” disconnect, invoke more complex tubing sets to allow the administration set to be flushed (often with antiseptic) prior to installation of dialysate and generally permit the patient to disconnect the empty bag during the dwell phase. Initial reports of the success of the protocols in reducing peritonitis were regarded with skepticism, but definite improvement over earlier systems has now been documented in a well-designed and carefully controlled clinical trials [Churchill et al., 1989].

Fluid and Solute Removal

The rate at which solutes are removed during peritoneal dialysis depends primarily upon the rate of equilibration between blood and instilled peritoneal fluid. This is usually quantified as the ratio of

TIME FROM ONSET OF EXCHANGE, mins

O

подпись: o

< ■ “—“—x

Q 0.00 —1 1 ‘ 1 1 1 1 1 1—1—1—1—1—■—1—1 ‘ ’—

0 60 120 180 240 300 360

подпись: 
< ■ “—“—x
q 0.00 —1 1 ' 1 1 1 1 1 1—1—1—1—1—■—1—1 ' ’—
0 60 120 180 240 300 360
FIGURE 131.3 Ratio of plasma to dialysate concentration for urea (60 daltons), creatinine (113 daltons), uric acid (158 daltons), and Q2 microglobulin (012,000 daltons). Data were obtained by withdrawing and analyzing a sample of dialysate at each time point and comparing it to plasma concentration. Each point is the average of two determi­nations on five patients. Error bars are standard error of the mean [Lysaght, 1989].

Dialysate to plasma concentration as a function of dwell time, often in graphs called simply “D over P” (dialysate over plasma) curves. A typical plot of dialysate-to-plasma ratio for solutes of various molecular weight is given in Fig. 131.3. Smaller species equilibrate more rapidly than do larger ones, because diffusion coefficient varies in inverse proportion to the square root of a solute’s molecular weight. Dialysate equilibrium rates vary considerably from patient to patient; error bars on the plot represent standard error of the mean for duplicate determinations with five patients.

The rate of mass removal during dialysis, □, is simply the volume of fluid, VD, removed from the peritoneal cavity at the end of a dwell period lasting time t, multiplied by the concentration CD of the solute in the removed fluid

= VDCD (131.1)

The whole blood clearance, Cl, is the rate of mass removal divided by the solute concentration in blood CB

Cl □ —□ (131.2)

TCB tCB

In Eqs. (131.1) and (131.2), time conventionally is reported in minutes, volume in milliliters, and concentration in any consistent units. Equations (131.1) and (131.2) are based on mass balances; they are thus general and unaffected by the complexity of underlying phenomena such as bidirectional selective connective transport and lymphatic uptake. Equation (131.2) requires that solute concentration in the denominator be reported as whole blood concentration, rather than as plasma concentration, which is

Often reported clinically. With many small solutes (urea, creatinine, and uric acid), only small error is

Introduced by considering blood and plasma concentration as interchangeable. With larger solutes,

Peritoneal Dialysis Equipment

FIGURE 131.4 Volume of fluid in the peritoneal cavity versus time during an exchange with 02.5% glucose dialysis fluid. Solid line is actual volume. Dotted line represents estimate of the volume in the absence of lymphatic flow. Results represent an average of duplicate determinations on five patients. Volume was estimated by dilution of radiolabeled tracers (too large to diffuse across the peritoneal membrane) added to dialysate prior to installation; lymphatic flow was calculated from a mass balance on net recovered marker. Each point is the average of two determinations on five patients. Error bars are standard error of the mean [Lysaght, 1989].

Especially those excluded from the red blood cell, care must be taken to correct for differences in plasma and blood concentrations.

Since urea is nearly completely equilibrated during CAPD, i. e., cD/cB = 01.0, urea clearance is commonly equated with total drainage volume. Four 2-L exchanges and 2 L of ultrafiltration would thus result in a continuous urea clearance of 10 L/day or 07 ml/min. The situation is more complex with APD, which involves several (4-6) short exchanges at partial equilibrium and one very long exchange. In any case, no meaningful direct or a priori comparison of clearance with hemodialysis is possible because one therapy is intermittent and the other continuous.

The volume of fluid in the peritoneal cavity increases during an exchange but at a decreasing rate. The driving force for fluid transfer from the blood to the peritoneal cavity is the osmotic pressure of the glucose in the infused dialysate. Typical CAPD solutions contain 01.5%, 02.5%, or 04.25% by weight of glucose monohydrate, leading to an initial maximum osmotic force (across an ideally semipermeable membrane) of approximately 1000-5000 mmHg. In the first few minutes of an exchange, the rate of ultrafiltration may be as high as 10-30 ml/min. The driving force rapidly dissipates as glucose diffuses from the peritoneal cavity into the bloodstream. After the first hour, rates of 1.0-2.0 ml/min are common. Throughout the exchange, the peritoneal lymphatics are draining fluid from the peritoneal cavity at a rate of 0.5-2.0 ml/min. Fluid balance is thus the difference between removal by a time-dependent rate of ultrafiltration and return via a more constant lymphatic drainage. Net fluid removal is very easily determined in the clinical setting simply by comparing the weight of fluid drained to that instilled. Instantaneous rates of ultrafiltration may be estimated in study protocols by a series of tedious mass balances around high-molecular-weight radiolabled markers added to the dialysate fluid. The results of a typical study are plotted in Figs. 131.4 and 131.5 Showing both the instantaneous rate of ultrafiltration and the net intraperitoneal volume as a function of time. On average, these patients removed 500 ml of fluid in a single 6-hour exchange or roughly 2 L/day, which permits far more liberal fluid intake than

Peritoneal Dialysis Equipment

FIGURE 131.5 Comparisons of rates of ultrafiltration of fluid into the peritoneal cavity (open circles) and lymphatic drainage of fluid from the peritoneal cavity back to the patient (dotted line). Same study and methods as in Fig. 131.4.

Is possible with patients on HD. But here again patient variation is high. Commercial CAPD fluid is available in a variety of solute concentrations; physicians base their prescription for a particular patient on his or her fluid intake and residual urine volume.

The Peritoneal Membrane: Physiology and Transport Properties

In contrast to synthetic membranes employed during HD, the peritoneum is not a simple selective barrier between two phases. As implied by its Latin root (peritonere = to stretch tightly around), the primary physiologic function of the peritoneum is to line the walls of the abdominal cavity and encapsulate its internal organs (stomach, liver, spleen, pancreas, and parts of the intestine). Most CAPD literature, including this review, uses the terms peritoneum and peritoneal membrane interchangeably and conve­niently extends both expressions to include underlying and connective tissue. Overall adult peritoneal surface is approximately 1.75 □ 0.5 m2, which generally is considered equal on an individual basis to skin surface area. The peritoneum is not physically homogenous. The visceral portion (080%) covering the internal organs differs somewhat from the parietal portion overlaying the abdominal walls, which in turn is different from the folded or pleated mesentery connecting the two.

The physiology of the peritoneum, its normal ultastructure, and variations induced by CAPD have been increasingly elucidated over the past decade. Morphologically, the peritoneum is a smooth, tough, somewhat translucent sheath. Its thickness ranges from under 200 to over 1000 microns. The topmost layer, which presents to the dialysate during CAPD, is formed from a single layer of mesothelial cells, densely covered by microvilli (hairlike projections), although the latter tend to disappear gradually during the first few weeks of CAPD. Immediately underneath is the interstitium, a thick sheath of dense mucopolysaccharide hydrogel interlaced with collagenous fibers, microfibrillar structures, fibroblasts, adipocytes, and granular material. Most important for CAPD, the interstitium is perfused with a network of capillaries through which blood flows from the mesenteric arteries and the vasculature of the abdominal wall to the portal and systemic venous circulations. Blood-flow rate has been estimated to be in the range of 30-60 ml/min, but this is not well established. The interstitial layer is a hydrogel; its water content, and thus its transport properties, will vary in response to the osmolarity of the peritoneal dialysate.

Peritoneal mass transfer characteristics are most commonly obtained by back-calculating basic mem­brane properties from results in standard or modified peritoneal dialysis. Three membrane parameters will be described: Lp, the hydraulic permeability; R, the rejection coefficient; and KoA, the mass transfer coefficient ( = area A □ diffusive permeability Ko). The formal definitions of these parameters are given in Eqs. (131.3) through (131.5), with R and KoA defined for the limiting conditions of pure convection and pure diffusion.

LP □ Fillrali°n rate =, (131.3)

Area ^pressure driving force A(P □ □□Q)

^, m Concentration in bulk filtrate m □ CD D

R □ 1 □ = (131.4)

Concentration in bulk retentate C„ fl

Y B MudD 0

K0A □ Solute transport = Dd □ (131.5)

Concentration driven force nC„ □ Cn M

Y B D Mifr□ 0

Where JF = filtration rate, A = area, □ = Staverman reflection coefficient, □ = osmotic pressure, and other terms are as defined previously.

At the onset of a CAPD exchange using 4.25% dextrose, the ultrafiltration rate is 10-30 ml/min. Relative to a perfectly semipermeable membrane, the glucose osmotic pressure of the solution is 4400 mmHg. Overall membrane hydraulic permeability is the quotient of these terms and is thus of the order of 0.2 ml/hr-mmHg, in the units commonly employed for HD membranes. This estimate needs to be corrected for the osmotic back-pressure, which is primarily due to urea in the blood (conc 0 1.3 g/L) as well as the fact that the membrane is only partially semipermeable. The best results are not obtained from a single point measurement but either from curve fitting to the ultrafiltration profile during the entire course of dialysis or from data taken at different osmotic gradients. A review [Lysaght & Farrell, 1989] of reports from several different investigators suggests an average value of 0 2 ml/hr-mmHg or, roughly, 2 gal/ft2/day (GSFD) at 100 PSI. This is higher than desalination membranes, just slightly lower than conventional regenerated cellulose hemodialysis membranes, and much lower than anisotropic ultrafiltration membranes.

Rejection coefficients, R, numerically equal to unity minus sieving coefficient are obtained either from kinetic modeling as described below or experimentally by infusing a hypertonic solution into the peri­toneum with a permeant concentration equal to that in the plasma. After a suitable period of ultrafil­tration, the ration of solute to water flux is calculated from the dilution of the recovered solution. Both methods are approximate and results from different investigators may vary substantially. Reported values are observed average rejection coefficients. These are often described as the Staverman rejection coeffi­cient, □, which is somewhat overreaching, since filtration velocity is not recorded and differences between bulk and wall concentrations are not known. Representative values, from a review of the literature [Lysaght & Farrell, 1989], are summarized in Table 131.1. Thus the membrane appears quite tight, possibly rejecting about 10-20% of urea and other small molecules, about 50% of intermediate-molec – ular-weight species, and over 99% of plasma proteins.

The diffusive permeability of the membrane is obtained by back calculation from measurements of blood and dialysate concentration versus time during an exchange, as will be further elaborated below. Values are given as the product of membrane permeability and estimated peritoneal area (KA), and the results of various investigators have been reasonably consistent. Critical values from a review of the literature are summarized in Table 131.1. A KoA value of about 20 ml/min for urea is around one order of magnitude less than comparable values for contemporary hollow-fiber hemodialyzers. If the area of the peritoneum is taken as 1.75 m2, then urea transfers through the peritoneum analogously to urea diffusing through a stagnant film of water roughly a centimeter thick. Alternatively, given a peritoneal

Permeant Species, MW

Rejection Coefficient, dimensionless

KjA cm3/min

Urea, 60

0.26 □ 0.08

21 □ 4

Creatinine, 113

0.35 □ 0.07

10 □ 2

Uric acid, 158

0.37

10

B-12, 1355

5

Inulin, 5200

0.5 □ 0.2

4 □ 1.5

□2microglobulin, 12,000

0.8 □ 0.4

Albumin, 69,000

0.99

Note: SD not given if n < 3. Equivalent ultrafiltration coefficient is D2.0 ml/min- m2-mmHg. Data taken from a review by Lysaght and Farrell [1989].

Thickness range of 200-2000 microns, the diffusion of urea inside the membrane is about 20% of what would be found in a film of stagnant water of the same thickness.

It should once more be noted that the physiologic peritoneum is a complex and heterogeneous barrier, and its transport properties would be expected to vary over different regions of its terrain. For example, studies in animal models have suggested that transport during peritoneal dialysis is little affected when large segments of the visceral membrane are surgically excised. It is also repeated for emphasis that the terms Lp, R, and KA do not describe this membrane itself but rather a hypothetical barrier that is functionally and operationally equivalent and thus capable of producing the same mass transfer charac­teristics in response to the same driving forces.

Transport Modeling

Several investigators have developed mathematic models to describe, correlate, and predict relationships among the time-course of solute removal, fluid transfer, treatment variables, and physiologic properties [Lysaght & Farrell, 1989; Vonesh et al., 1991; Waniewski et al., 1991]. Virtually all kinetic studies start with the model illustrated in Fig. 131.6. THe patient is considered to be a well-mixed compartment with a distribution volume VB set equal to some fraction of total body weight. (For example, urea distributes over total body water, which is □ 0.58 times body weight.) Dialysate occupies a second, much smaller compartment, VD = 2-3 L, which is also considered well-mixed but which changes in size during the

Lymph Flow

1

C

VBC8

Patient

3

I

1

1

C

JF

J v°

0s

Peritoneal

»

C„

Cavity

Fixed Volume Variable Volume

Peritoneal Membrane (Lp, a-, KoA)

FIGURE 131.6 Single pool model for peritoneal dialysis. Solute diffuses across a planar selective membrane from a large well-mixed plasma space at constant volume and concentration to a smaller well-mixed space in which concentration and volume both increase with time. Fluid and solute are selectively ultrafiltered across the peritoneal membrane from plasma to dialysate; they are also nonselectively transported by the lymphatics from the dialysate to the body compartment.

Course of exchange. These two compartments are separated by a planar membrane capable of supporting bidirectional transport and characterized by the terms Lp, R, and KoA previously defined by Eqs. (131.3)—(131.5). Fluid drains from the peritoneum to the blood at a rate of QL. From this point forward, the complexity and appropriate utility of the models depend upon the investigators’ choices of simplifying assumptions. The simplest model, proposed by Henderson and Nolph [1969], considers ultrafiltration rate and lymphatic flow to be negligible and treats all parameters except dialysate concen­tration as constant with time. The basic differential equation describing this model is

Peritoneal Dialysis Equipment

(131.6)

Peritoneal Dialysis Equipment

K0 A □-

подпись: k0 a □-Equation 131.6 may be readily solved, either to obtain KoA from a knowledge of concentration versus time data Eq. (131.7), or to predict dialysate concentration from a knowledge of mass transfer coefficient, blood concentration, and initial dialysate concentration Eq. (131.8) where:

(131.7)

□ K 0At

Peritoneal Dialysis Equipment

(131.8)

In these equations, the superscript t represents the value at time t, and the superscript 0 designates the

Value at t = 0. This model provides a very easy way of measuring K0A if it is applied during the isovolemic interval that often occurs □ 30-90 min after the beginning of an exchange.

Several years later, investigators at the University of New South Wales [Garred et al., 1983] proposed a slightly more complex model that included ultrafiltration, subject to the assumptions that: (1) blood concentration was constant, (2) the membrane was nonselective (R = O), and (3) lymphatic involvement could be ignored. The appropriate differential equation is now:

Peritoneal Dialysis Equipment

(131.9)

Peritoneal Dialysis EquipmentThis equation can be solved in two ways. Over either relatively short time intervals or small differences in dialysate volume, an average volume VD is obtained as the mean of initial and final volumes. In that case K0A is given by

(131.10)

Where variables overlined with a solid diachrin are treated as constant during the integration of Eq. (131.9). The similarity of Eqs (131.9) and (131.10) to Eqs. (131.7) and (131.8) should be noted. Where a series of data points for blood and dialysate concentrations are available at various times during the treatment, Eq. (131.10) may be rewritten as

□□ KaAt □

Peritoneal Dialysis Equipment

D

Infc ( □ CD) ln[ ( □ CD) ]

VD

Data in the form of this equation may be readily regressed to obtain K0A from a knowledge of VD, CB, and CD at various times in an exchange. The values for peritoneal volume VD may be obtained experi­mentally from tracer dilution studies, calculated from an algorithm, in which case it varies with time, or simply averaged between initial and final values, in which case it is assumed constant. Equations (131.11) and (131.12) are recommended for routine modeling of patient kinetics.

Several investigators, reviewed by Lysaght and Farrell [1989], have produced far more elaborate models which incorporate lymphatic drainage, deviations from ideal semipermeability of the peritoneal mem­brane, time-dependent ultrafiltration rates, and coupling between bidirectional diffusive and connective transport. Although potent in the hands of their developers, none of the numerical models has been widely adopted, and the current trend is toward simpler approaches. In comparative studies [Lysaght, 1989; Waniewski et al., 1991], only small differences were found between the numeric values of transport parameters calculated from simple analytic models [Eqs. (131.6)—(131.12)] and those we obtained by far more complex numerical methods. In peritoneal dialysis, solute is being exchanged through an inefficient membrane between a large body compartment through an inefficient membrane and a second compart­ment only 5% as large, and treatment times have been chosen so that the smaller compartment will reach saturation. These physical circumstances, and the very forgiving nature of exponential asymptotes, perhaps explain why simple analytic solutions perform nearly as well as their more complex numeric counterparts.

Emerging Developments

Modified therapy formats and new formulations for exchange solutions constantly are being proposed and evaluated. APD is the most successful of the new formats; at the end of 1993, about one in six peritoneal dialysis patients received some variant of automated overnight treatment. APD is carried out by a small console (Fig. 131.7) Which automatically instills and drains dialysate at 1.5—3-hour intervals while the patient sleeps, typically over 8—10 hours each night. The peritoneum is left full during the day. Since the short exchanges do not permit complete equilibration even for urea, the process is somewhat wasteful of dialysate. However, reference to Fig. 131.3 wIll readily demonstrate that small-solute removal is most efficient in the early portion of an exchange; for example, two 2-hour exchanges will provide 75% more urea clearance than one 4-hour exchange. As currently prescribed, APD requires 84—105 L per week of dialysate (versus 56 for CAPD) and increases total small-solute clearance per 24 hours by up to 50% over that achieved by CAPD. The number of patients on APD is increasing by half every year, a phenomenon driven by two main factors. The first relates to quality of life; APD is far-and-away the least invasive of the maintenance dialysis protocols. The patient performs one connection at night and one disconnection in the morning and is thereby freed from the tedium and inconvenience of daily exchanges or the need to spend a significant portion of 3 days per week at an HD treatment facility. In addition, small-solute clearance is higher than in other continuous peritoneal therapies, which helps address increasing concern about the adequacy of the standard four 2-L CAPD exchanges per day, especially with large muscular patients and those with no residual renal function. A group of patients who may benefit from APD are those who have rapid transport of glucose across the peritoneal mem­brane; because of the consequent loss of the osmotic gradient, they have difficulty achieving adequate ultrafiltration. The short dwell times of ADP circumvent this problem. The counterbalancing disadvan­tage of APD is increased expense associated with the larger fluid consumption and the fluid cyclers.

Virtually all solution development comprises attempts to replace glucose with an alternative osmotic agent, preferably one which diffuses more slowly and thus provides a more stable osmotic gradient and one which obviates the obligatory load of about 600 calories of sugar. However glucose is cheap and safe, and it will be difficult to find a satisfactory alternative. A competing osmotic agent must be safe to

Peritoneal Dialysis Equipment

FIGURE 131.7 Contemporary equipment module for APD (Home Choice, Renal division, Baxter Healthcare) which automatically controls and monitors the delivery of 10-15 L of dialysate from 5-L bags via a multipronged disposable administration set. The console incorporates a diaphragm pump used to emulate gravity, and a derivative of the ideal gas law measures fluid volume, eliminating the need for scales. Setup and operation are designed to be straightforward and convenient.

Administer in amounts of tens of grams per day over years to patients who have little or no ability to clear accumulated material via the kidney—but an osmotic agent which is readily metabolizable provides no caloric “advantage” over glucose. A glucose polymer, termed polyglucose, has been recently introduced in England [Mistry & Gokal, 1993]. This disperse oligodextrin has a weight-averaged MW of 18,700 daltons and number-averaged molecular weight of 7300 daltons. At a concentration of 7.5% (i. e., 30 g per 2-L exchange), it provides more stable ultrafiltration during long dwell exchanges; however, admin­istration is limited to one exchange per day because of the accumulation of maltose and higher MW polysaccharides; an alternative approach, recently introduced in Europe and in clinical trials in the United States, is a solution in which glucose is replaced with 1.1% amino acids, enriched for essential amino acids [Jones et al., 1992]. This solution also improves nitrogen balance, a significant feature, since dialysate patients are frequently malnourished. Concern about excessive nitrogen intake, however, limits its use to one or two exchanges per day, and the amino acid solution is necessarily more expensive than glucose.

Defining Terms

Automated peritoneal dialysis (APD): A recent variant of CAPD in which fluid exchanges are per­

Formed by simple pumps, usually at night while the patient sleeps.

Clearance: The rate of mass removal divided by solute concentration in the body. Clearance represents

The virtual volume of blood or plasma cleared of a particular solute per unit time.

Continuous ambulatory peritoneal dialysis (CAPD): A continuous process for the treatment of

Chronic renal failure in which metabolic waste products and excess body water are removed through the peritoneum with four exchanges of up to 3 L every 24 hours.

Diffusion: The molecular movement of matter from a region of greater concentration to lesser con­

Centration at a rate proportional to the difference in concentration.

Hemodialysis (HD): Intermittent extracorporeal therapy for chronic renal failure. See Chapter 130.

Mass transfer coefficient: The proportionality constant between the rate of solute transport per unit

Area and the driving force.

Membrane: A thin barrier capable of providing directional selective transport between two phases.

Peritoneal cavity: A topologically closed space in the abdomen which is surrounded by the peritoneum.

Peritoneum: An intricate, vascularized, membranelike tissue that lines the internal abdominal walls

And covers the liver, intestine, and other internal organs. Used interchangeably with the expression peritoneal membrane.

References

Boen ST. History of peritoneal dialysis.1985. In KD Nolph (ed), Peritoneal Dialysis, pp 1—22, The Hague, Martinus Nijhoff.

Churchill DN, Taylor DW, Vas SI, et al. 1989. Peritonitis in continuous ambulatory peritoneal dialysis (CAPD): A multi-centre randomized clinical trial comparing the Y connector disinfectant system to standard systems. Perit Dial Int 19:159.

Dratwa M, Collart F, Smet L. 1986. CAPD peritonitis and different connecting devices: A statistical comparison. In JF Maher, JF Winchester (eds), Frontiers in Peritoneal Dialysis, pp 190—197, New York, Field Rich.

Garred LJ, Canaud B, Farrell PC. 1983. A simple kinetic model for assessing peritoneal mass transfer in chronic ambulatory peritoneal dialysis. ASAIO J 6:131.

Henderson LW, Nolph KD. 1969. Altered permeability of the peritoneal membrane after using hypertonic peritoneal dialysis fluid. J Clin Invest 48:992.

Jones MR, Martis L, Algrim CE, et al. 1992. Amino acid solutions for CAPD: Rationale and clinical experience. Miner Electrolyte Metab 18:309.

Lysaght MJ. 1989. The Kinetics of Continuous Peritoneal Dialysis. PhD thesis, Center for Biomedical Engineering, University of New South Wales.

Lysaght MJ, Farrell PC. 1989. Membrane phenomena and mass transfer kinetics in peritoneal dialysis. J Mem Sci 44:5.

Mistry CD, Gokal R. 1993. Single daily overnight (12-h dwell) use of 7.5% glucose polymer (Mw 18700;

Mn 7300) + 0.35% glucose solution: A 3-month study. Nephrol Dial Transplant 8:443.

Popovich RP, Moncrief JW, Decherd JF, et al. 1976. The definition of a novel portable/wearable equilib­rium peritoneal technique. Abst AM Soc Artif Intern Organs 5:64.

Vonesh EF, Lysaght MJ, Moran J, et al. 1991. Kinetic modeling as a prescription aid in peritoneal dialysis. Blood Purif 9:246.

Waniewski J, Werynski A, Heimburger O, et al. 1991. A comparative analysis of mass transport models in peritoneal dialysis. ASAIO Trans 37:65.

Further Information

The literature on continuous peritoneal dialysis is abundant. Among several reference texts the most venerable and popular is Peritoneal Dialysis edited by K. Nolph and published by Kluwer; this is regularly updated. Also recommended is Continuous Ambulatory Peritoneal Dialysis edited by R Gokal and pub­lished by Churchill Livingston. The journal Peritoneal Dialysis International (published by MultiMed; Toronto) is published quarterly and is devoted exclusively to CAPD. The continuing education depart­ment of the University of Missouri-Columbia organizes a large annual conference on peritoneal dialysis with plenary lecture and submitted papers. The International Society of Peritoneal Dialysis holds its conference biannually and usually publishes proceedings. Peritoneal dialysis is also discussed in the meeting and journals of the other major artificial organ societies (American Society of Artificial Internal Organs; European Dialysis and Transplant Association; Japanese Society of Artificial Organs) and the American and International Societies of Nephrology. Blood Purification (published by Karger; Basel) attracts many outstanding papers dealing with engineering and transport issues in peritoneal dialysis. For the insatiable, Medline now contains over 10,000 citations to CAPD and peritoneal dialysis.

Zydney, A. L. “Therapeutic Apheresis and Blood Fractionation.” The Biomedical Engineering Handbook: Second Edition.

Ed. Joseph D. Bronzino

Boca Raton: CRC Press LLC, 2000

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