What is Peritoneal Dialysis?

In essence, peritoneal dialysis involves the transport

of solutes and water across a membrane that separates two fluid-containing compartments. These two compartments are (a) the blood in the peritoneal capillaries, which in renal failure contains an excess of urea, creatinine, and other solutes, and (b) the dialysis solution in the peritoneal cavity, which typically contains sodium, chloride, and lactate or bicarbonate and which is rendered hyperosmolar by the inclusion of a high concentration of glucose. During the course of a peritoneal dialysis dwell, three transport processes occur simultaneously: Diffusion, 4/22/12 ultrafiltration, and absorption. The amount of dialysis

Anatomy of the Peritoneal Cavity

The peritoneum is the serosal membrane that

lines the peritoneal cavity. It has a surface area that is thought to be approximately equal to body surface area and so typically ranges from 1 to 2 m2 in an adult. It is divided into two portions: (a) the visceral peritoneum, which lines the gut and other viscera, and (b) the parietal peritoneum, which lines the walls of the abdominal cavity.

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The visceral peritoneum accounts for about 80% of the total peritoneal surface area and receives its blood supply from the superior mesenteric artery, whereas its venous drainage is via the portal system. In contrast, the parietal peritoneum, which may be more important in peritoneal dialysis, receives blood from the lumbar, intercostal, and epigastric arteries and drains into the inferior vena cava. Total peritoneal blood flow cannot be directly measured but has been indirectly estimated at between 50 and 100 mL per minute. The main lymphatic drainage of the peritoneum and of the peritoneal cavity is via stomata in the 4/22/12 diaphragmatic peritoneum, which ultimately

Models of Peritoneal Transport

Simplistically, the peritoneal membrane can

be thought of as comprising six resistances to solute transport: (a) the stagnant capillary fluid film overlying the endothelium of the peritoneal capillaries, the capillary endothelium itself, (c) the endothelial basement membrane, (d) the interstitium, (e) the mesothelium, and (f) the stagnant fluid film that overlies the mesothelium. Of these, a, e, and f (stagnant fluid films and the mesothelial layer) are thought to offer only trivial resistance to transport. Two concepts of 4/22/12

The Three Pore Model

clinical observations, tells us that the peritoneal capillary is the critical barrier to peritoneal transport, and that solute and water movement across it is mediated by pores of three different sizes. These are:

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Large pores with a radius of 20 - 40 nm. Macromolecules such as protein are transported by convection through these pores, which correspond to large clefts in the endothelium. Small pores with a radius of 4.0 - 6.0 nm. There are a large number of these, which also likely represent interendothelial clefts; they are responsible for the transport of small solutes, such as urea, creatinine, sodium, and potassium, in association with water. Ultrapores with a radius of <0.8 nm. These are responsible for the transport of water only 4/22/12 and are thought to correspond to aquaporins,

Distributed Model and Effective Peritoneal Surface Area The distributed model emphasizes the

importance of the distribution of capillaries in the peritoneal membrane and of the distance water and solutes have to travel from the capillaries across the interstitium to the mesothelium. Transport is dependent on the surface area of the peritoneal capillaries rather than on the total peritoneal surface area. Furthermore, the distance of each capillary from the mesothelium determines its relative contribution. The cumulative contribution of all of the peritoneal capillaries 4/22/12

Diffusion
Uremic solutes and potassium diffuse from

peritoneal capillary blood into the peritoneal dialysis solution, whereas glucose, lactate or bicarbonate, and, to a lesser extent, calcium diffuse in the opposite direction. Peritoneal diffusion depends on the following factors:

The concentration gradient. For a

substance such as urea, this is maximal at the start of a peritoneal dialysis dwell, when the concentration in the dialysis solution is zero. It gradually decreases during the course of the 4/22/12 dwell. The diminishing concentration gradient

Molecular weight of the solute concerned.

Substances with lower molecular weight, such as urea (MW 60), are more quickly transported by diffusion than those with higher molecular weights, such as creatinine (MW 113) or albumin (MW 69,000).
Mass transfer area coefficient. The combined

effects of factors 2 - 4 are sometimes measured by an index called the mass transfer area coefficient (MTAC), which is analogous to the K0A of a hemodialysis membrane. For a given solute, the 4/22/12 MTAC is equivalent to the diffusive clearance

Ultrafiltration
This occurs as a consequence of the osmotic

gradient between the hypertonic dialysis solution and the relatively hypotonic peritoneal capillary blood. It is driven by the presence of high concentrations of glucose in dialysis solution and depends on the following:

Concentration gradient for the osmotic

agent (i.e., glucose). Again, this is typically maximal at the beginning of a peritoneal dialysis dwell and decreases with time due to dilution of the glucose by ultrafiltrate and due 4/22/12 to diffusion of glucose from the dialysis

Hydraulic conductance of the peritoneal

membrane. This differs from patient to patient and perhaps reflects the density of small pores and ultrapores in the peritoneal capillaries, as well as the distribution of capillaries in the interstitium.

Reflection coefficient for the osmotic

agent (i.e., glucose). This measures how effectively the osmotic agent diffuses out of the dialysis solution into the peritoneal capillaries. It is between 0 and 1; the lower 4/22/12value, the faster the osmotic gradient is the

Oncotic pressure gradient. Oncotic

pressure acts to keep fluid in the blood, and so opposes ultrafiltration. In hypoalbuminemic patients, oncotic pressure is low, and ultrafiltration tends to be high.

Sieving. Sieving occurs when solute moves

along with water across a semipermeable membrane by convection, but some of the solute is held back, or sieved. As a result, the solute concentration in the ultrafiltrate that has passed through the membrane is lower 4/22/12 that in the source solution. When sieving than

Continuous Ambulatory Peritoneal Dialysis

present in the abdomen. The solution is typically changed four times daily, with a range of three to five times depending on individual patient requirements. Drainage of spent dialysate and inflow of fresh dialysis solution are performed manually, using gravity to move fluid into and out of the peritoneal cavity. Technically, PD solution flows into the peritoneal cavity, and dialysate drains out (i.e., the solution does not become dialysate until dialysis has occurred, although 4/22/12

Dialysis Solutions
CAPD solutions are packaged in clear, flexible

plastic bags or, less commonly, in semirigid plastic containers. The bags are typically made from polyvinyl chloride though theoretical concern about phthalic acid leachates have led to bags of other composition being developed. Some new PD solutions are packaged with the different solution components in two- (or three-) chamber bags, which are mixed before infusion into the peritoneal cavity.

4/22/12 Dialysis solution volumes. For adult

Dialysis solution electrolyte

concentrations. The electrolyte concentrations of CAPD solutions vary little by manufacturer. The standard formulations from the three large international manufacturers are shown in Table 19-1. Solutions contain no potassium and sodium levels are set at about 132134 mM. Higher sodium concentrations would lead to less diffusive removal of sodium during dwells. Low-sodium solutions have been proposed as a means of augmenting sodium removal but would likely lead to 4/22/12

 Dialysis solution dextrose concentrations. Dextrose (glucose

monohydrate, MW 198) is the osmotic agent commonly used in CAPD solutions, and preparations containing 1.5%, 2.5%, and 4.25% dextrose are routinely available and are labeled as such in North America. The true anhydrous glucose (MW 180) concentrations in these solutions are 1.36%, 2.27%, and 3.86%, respectively, and this is how they are typically labeled in Europe. The approximate osmolarities of these solutions are 345, 395, and 484 mOsm/L, respectively. An interesting preparation from Gambro is the tricompartmental Gambrosol Trio solution bag, which has one main compartment containing the solution and two other small compartments containing concentrated dextrose. This allows the osmolarity of the final infused solution to be varied. Opening the connection between one dextrose compartment and the rest of the bag gives a 1.5% solution. Opening the alternative dextrose compartment gives a 2.5% solution and opening both gives 3.9%. This avoids the need to store multiple different solution strengths but does increase complexity somewhat. This solution has the additional advantage of allowing the dextrose compartment solutions to be sterilized separately and at a lower pH than the usual 5.5 used for standard CAPD solutions. This minimizes caramelization of glucose and generation of toxic 4/22/12 degradation products (GDPs), which are increasingly believed to glucose

Nondextrose solutions. Dextrose as an

osmotic agent in PD has the advantage of being familiar, relatively safe, and inexpensive, and also is a source of calories. There is concern, however, that it predisposes patients to hyperglycemia, dyslipidemia, obesity, and long-term peritoneal membrane damage, both directly and via GDPs and advanced glycosylation end products that result from their metabolism. In addition, it is not very effective in some patients, especially high 4/22/12 transporters, and inadequate

Dialysis solution pH. In the manufacturing

process, the pH of traditional lactate-based PD solutions is lowered to about 5.5 to prevent caramelization of glucose and to minimize generation of GDPs during heat sterilization. Lowering pH further would decrease GDPs even more but would also cause infusion pain in patients. A pH of 5.5 on infusion is normally well tolerated, and rises rapidly as bicarbonate diffuses into the peritoneal cavity from the plasma. However, some patients complain of pain during inflow of dialysis 4/22/12

GDPs. As mentioned above, the heat

sterilization process leads to generation of GDPs, which have toxic effects on the peritoneal membrane. The principal strategy to deal with this is the use of multicompartmental solution bags where the glucose, having been heat-sterilized at a very low pH that retards the formation of GDPs (e.g., pH 3.2), is kept separate from the rest of the solution, which can then be maintained at an alkaline pH. At the time of use, the glucose is allowed to mix with the rest of the solution, 4/22/12

Sterility and trace metals. The preparation

of PD solutions is carefully regulated to ensure that the final product is bacteriologically safe and has very low concentrations of trace metals.

Dialysis solution temperature. PD

solutions are usually warmed to body temperature prior to inflow. They can be instilled at room temperature, but uncomfortable lowering of the body temperature and shivering can result. The 4/22/12 warming method is to use a heating pad best

Transfer Sets
The CAPD solution bag is connected to the

patient's peritoneal catheter by a length of plastic tubing called a transfer set (also sometimes called a giving set). There are three major types of transfer sets, each requiring a different method of performing the CAPD exchange. For the purpose of discussion, we will refer to them as the straight transfer set, the Y transfer set, and the double-bag system.

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Straight Transfer Set

associated with high rates of peritonitis. However, a brief description is helpful in understanding how more modern systems have evolved.
Design. The straight transfer set is a simple

plastic tube. One end connects to the peritoneal catheter and the other end to the dialysis solution bag. All exchanges are performed by making and subsequently breaking the connection between the transfer set and the bag. This connection typically involves a spike or 4/22/12 a Luer lock.

The Y-set

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Design. This is a Y-shaped piece of tubing

that is attached by its stem to the patient's catheter or extension tubing at the time of each solution exchange. During the exchange, the afferent and efferent limbs of the Y are attached to a bag of fresh PD solution and to a drain bag, respectively. In some cases, the drain bag is the empty solution bag that was used in the previous exchange. Most Y sets are not connected directly to the catheter but rather to a short (15 - 24 cm) extension tubing inserted between the catheter and the stem 4/22/12

Exchange procedure

Spike/lock: The fresh bag of PD solution is attached to the afferent limb of the Y set via a spike or Luer lock. Connect: The stem of the Y set is connected to the extension tubing. Drain: The stem and efferent limb of the Y are unclamped and the spent dialysate is drained from the peritoneal cavity into the drain bag. Flush: With the stem of the Y set clamped, approximately 100 mL of fresh solution is flushed from the new bag through the afferent limb of the Y into the efferent limb and so into the drain bag. Fill: The efferent limb is clamped and the stem unclamped, and the peritoneal cavity is filled from the new bag of PD solution.

Disconnect: The Y set is then disconnected from the extension tubing. The Y set was developed to free patients from the requirement to remain attached to the transfer set and empty bag between exchanges. Early studies revealed a more important benefit a peritonitis rate significantly lower than that with the straight set. This is thought to be due to the flush-before-fill procedure used to prime the tubing. Bacteria that may be introduced during the connection procedure are washed out of the Y set into the empty drainage bag rather than into the patient, as happens with the straight set. Also, because the tubing and bags are disconnected from the patient between exchanges, less mechanical stress may be placed on the catheter exit site and tunnel. This may result in fewer episodes of minor trauma to the catheter exit site and tunnel and therefore to fewer exit site and tunnel infections and associated peritonitis. because of this lower peritonitis rate and the convenience of allowing the patient to disconnect between exchanges, Y-set systems increasingly displaced the straight system as the transfer set of choice from the mid-1980s which are filled with sodium hypochlorite between exchanges, 4/22/12on. Nondisconnect Y sets,are now less so due to their complexity, lack of apparent additional were initially popular but

Double Bag Systems

set, in which the solution bag comes preattached to the afferent limb of the Y, so obviating the need for any spike or Luer lock connection. The drain bag is similarly preattached to the efferent limb, and the only connection the patient needs to make is thus between the transfer set and the extension tubing. A flush-before-fill step is still performed, but the purpose is only to flush out residual air and not to prevent peritoneal cavity contamination, as this is no longer relevant in the absence of a need to make a transfer set to a 4/22/12solution bag connection.

Exchange procedure

Connect: The patient connects the new transfer set to the extension tubing. Drain: The stem and efferent limb are unclamped and spent dialysate is drained from the peritoneal cavity into the drain bag. Flush: The stem is clamped, and the afferent limb of the Y is opened by breaking a frangible in the tubing. Then 100 mL of PD solution is flushed through from the fill bag to the drain bag to remove residual air from the tubing.

Fill: The efferent limb is clamped, the stem is 4/22/12unclamped, and fresh PD solution is run into the

Automated Peritoneal Dialysis

growing PD modality, and in some countries, including the United States, the majority of PD patients are treated this way. APD is traditionally divided into continuous cycling peritoneal dialysis (CCPD) and nocturnal intermittent peritoneal dialysis (NIPD), although the combination of cycler therapy at night with daytime exchanges is commonly used today. In CCPD, the patient carries PD solution in the abdominal cavity throughout the 4/22/12day but performs no exchanges and is not

Cyclers
These are machines that automatically cycle

dialysis solution into and out of the abdominal cavity. Contemporary cyclers are not gravity dependent but instead use hydraulic pumps to deliver the solution from 3-, 5-, or 6-L bags to a fill bag and from there into the abdomen. The solution in the fill bag is warmed before inflow. With the aid of pressure alarms, clamps, and timers, inflow, dwell, and outflow of solution are regulated and overfilling prevented.

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Dialysis Solution
Dialysis solution for APD is the same as that

used for CAPD. Most cyclers are fed by a tube containing a multipronged manifold that can attach to as many as eight dialysis solution containers simultaneously to provide sufficient solution for the night. The total number of containers required, and thus the cost, can be reduced by using large containers holding 3, 5, or 6 L of dialysis solution, although lifting these can be a problem for older and frailer patients. Because the cycler can 4/22/12 be fed from two or more containers

APD Connections
Transfer sets. One set of plastic tubing

serves to interconnect several solution containers to the cycler and to connect the cycler to the patient. Shorter, simpler, and less expensive solution delivery sets are constantly being developed.

Catheter transfer set connection. The

catheter transfer set connection must be made every night and broken every morning. Previously, many patients had a standard Luer lock connector at the end of the peritoneal 4/22/12 catheter. The procedure for connecting the

Tidal Peritoneal Dialysis

solute clearance by leaving a large volume of dialysis solution in the peritoneal cavity throughout the dialysis session. It was thought that this would allow diffusive clearance to continue throughout the cycling period. Initially, the peritoneal cavity is filled with a volume of solution selected to be as large as possible without causing discomfort. The volume used depends on patient size and habitus but is typically 2 to 3 L. When TPD was introduced, a 50% tidal volume was common; 4/22/12

Technical problems. Classical high-volume

TPD has a number of technical problems, making it difficult to recommend for routine use. Therefore, mainly low-volume TPD is currently used.

Peritoneal catheter. For classical high-volume

TPD with 2030 L of solution, the peritoneal catheter must have excellent inflow and drain characteristics, as flow must be 180 - 200 mL per minute during the drain phase. In contrast, low-volume TPD is often indicated to avoid alarms from low drain when the catheter 4/22/12 function is poor.