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                                               Peritoneal Dialysis
CORE CURRICULUM IN NEPHROLOGY                                                                         1083

  ● Peritoneo...
1084                                                                          TEITELBAUM AND BURKART

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CORE CURRICULUM IN NEPHROLOGY                                                                          1085

Peritoneal M...
1086                                                                             TEITELBAUM AND BURKART

solutions (as a ...
CORE CURRICULUM IN NEPHROLOGY                                                                          1087

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1088                                                                                 TEITELBAUM AND BURKART

CORE CURRICULUM IN NEPHROLOGY                                                                           1089

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1090                                                                            TEITELBAUM AND BURKART

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CORE CURRICULUM IN NEPHROLOGY                                                                         1091

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CORE CURRICULUM IN NEPHROLOGY                                                                         1093

patients who ...
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     spontaneous re...
CORE CURRICULUM IN NEPHROLOGY                                                                     1095

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1096                                                                                        TEITELBAUM AND BURKART

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  1. 1. CORE CURRICULUM IN NEPHROLOGY Peritoneal Dialysis Isaac Teitelbaum, MD, and John Burkart, MD ● Chronic Use Catheters: A T THE END OF the millennium, there were 275,053 dialysis patients in the United States. Of these, 5.2% were on continuous ambu- Standard chronic indwelling PD catheters are made of soft materials, such as silicone rubber or latory peritoneal dialysis (CAPD) and 4% on polyurethane. automated peritoneal dialysis (APD). The num- ● Silicone rubber is used most frequently, ber of incident peritoneal dialysis (PD) patients relatively biocompatible, inert, no leachable using automated forms of PD, now estimated to plasticizers be over 40%, has been increasing. In contrast to ● Polyurethane catheters: better wall strength, the experience in the United States, the number however, cracking of the catheter has been of prevalent end-stage renal disease patients on reported after use of topical polyethylene PD in other countries reaches as high as 60%. glycol, alcohol, or mupirocin Reasons for differences are multifactorial and ● Design Modifications: include, but are not limited to, access to PD, ● Straight PD catheters were associated with a physician comfort/expertise with therapy, and high rate of external cuff extrusion and government reimbursement policies. catheter migration ● “Swan-neck” catheter: lateral or downward external exit and a permanent bend in the COMPONENTS OF THE PERITONEAL subcutaneous portion DIALYSIS SYSTEM ● Most catheters exit at the lateral abdominal Renal replacement therapy with PD requires 3 wall, however, one modification uses a prest- key components: (1) the PD catheter, (2) PD ernal exit site (thought to be subject to less solutions, and (3) the peritoneal membrane and trauma and allows patients to “immerse” in its associated vascular supply. water) ● Catheter Implantation Techniques: Catheter Issues Implantation technique significantly influ- ● Acute Use Catheters: ences long-term patient outcome. ● Straight, relatively rigid conduits about 3 ● Sterile conditions are essential mm in diameter and 25 to 30 mm in length ● Experienced catheter insertion team designed for short-term (2 to 3 days) use ● A panel of experts has agreed on 5 general ● Can be placed at the beside standards for catheter placement: ● Significant risk of peritonitis, malfunction, (1) the deep cuff should be in the anterior and bowel perforation abdominal musculature; ● Seldom used (2) the subcutaneous cuff should be near the skin surface and not less than 2 cm from the exit site; From the University of Colorado School of Medicine, (3) the catheter exit should be positioned lat- University of Colorado Hospital, Denver, CO; and Outpa- erally; tient Dialysis Services, Wake Forest University Baptist Medi- (4) the exit site should be directed downward cal Center, Winston Salem, NC. Address reprint requests to Isaac Teitelbaum, MD, Profes- or laterally; and sor of Medicine, University of Colorado School of Medicine, (5) the intra-abdominal portion should be Director, Home Dialysis Program, University of Colorado placed between the visceral and parietal Hospital, 4200 East 9th Ave, Denver, CO 80262. E-mail: peritoneum. ● Surgical insertion of catheters—most com- © 2003 by the National Kidney Foundation, Inc. 0272-6386/03/4205-0034$30.00/0 monly used placement procedure in clinical doi:10.1053/S0272-6386(03)01123-5 practice today 1082 American Journal of Kidney Diseases, Vol 42, No 5 (November), 2003: pp 1082-1096
  2. 2. CORE CURRICULUM IN NEPHROLOGY 1083 ● Peritoneoscopic insertion: allows direct vi- concentrations of 98 to 120 mEq/L (mmol/ sualization of the course of the catheter L). Preliminary studies show an increase in ● Blind placement: does not allow direct visu- net Na loss and better volume and blood alization of the catheter or peritoneum pressure control. ● should not be used in markedly obese pa- ● Potassium: Potassium is usually not added tients to chronic PD fluids. Patients tend to lose ● should be used in those who have had previ- about 35 to 40 mEq/day in the dialysate ous abdominal surgery while maintaining a serum K concentra- ● Moncrief-Popovich technique: incorporates tion of approximately 4.0 mEq/L (mmol/L). 2 modifications of conventional implanta- ● Magnesium: Dialysis solutions with an Mg2 tion procedures concentration of 0.5 mEq/L are now widely ● At time of implantation, the entire extraperi- used. toneal portion of the catheter is placed sub- ● Calcium: Historical dialysate fluids con- cutaneously tained Ca2 concentrations of 3.5 mEq/L. If ● At a subsequent date (4 to 6 weeks after calcium salts were used as a phosphate implantation), the external portion of the binder, hypercalcemia (in 35% to 56% of catheter is exteriorized, so that dialysis can patients) and metastatic calcification were be initiated immediately frequently noted. Because of these compli- ● Catheter Break-In: Normal to flush the peri- cations, dialysis fluids were developed with toneal cavity with between 500 and 1,500 a lower, nearly physiologic Ca2 concentra- mL of dialysis fluid until clear immediately tion (2.5 mEq/L). With these fluids, there is postplacement a risk of net Ca2 loss in some patients, ● Heparin (500 to 1,000 U/L) can be added in resulting in negative Ca2 balance and an cases where fibrin is present increase in parathyroid hormone levels. ● Optimally, PD should not be initiated until ● Buffers 10 to 14 days after catheter placement ● Most commercially available PD fluids con- ● If PD must be started immediately postim- tain a racemic mixture of both D- and L- plantation or before optimal catheter break- lactate as the buffer. Solutions have been in, use intermittent dialysis with low dialy- sate volumes (ie, 1,500 mL) in the supine very functional with patients surviving on position PD for up to 20 years. ● Lactate-containing fluids are “bioincompat- ● Catheter Survival: Transfer from PD to hemodialysis due to catheter-related prob- ible”—all normal cellular functions of resi- lems in about 20% of cases dent peritoneal cells are impaired; clinical ● Often due to a catheter infection–related issue significance unknown. ● Occasionally due to catheter migration and ● Bicarbonate-based buffer system would be to dialysate leaks preferable but has been associated with many ● 3-year catheter survival rate of 80% should problems including precipitation of Ca2 be expected, with a minimally acceptable and Mg2 carbonates; caramelization of glu- rate of 80% at 1 year cose at physiologic pH during sterilization. ● To avoid these problems, a 2-chamber bag Dialysis Solutions in which the 2 solutions are combined at the ● Electrolytes time of use has been developed. ● Sodium: Sodium has been added to the ● Osmotic Agents dialysis in varying concentrations ranging Several substances have been tried as osmotic from 120 to 140 mEq/L (mmol/L), most agents. These include both low molecular weight have a Na concentration of 132 mEq/L (glucose, glycerol, sorbitol, amino acids, xylitol, (mmol/L). Some studies have focused on and fructose) and high molecular weight (glu- the use of lower dialysate Na concentra- cose polymer, gelatin, polycation, dextrans, and tions to facilitate salt and water loss to better polypeptides) agents. At present, glucose re- control hypertension, using dialysate Na mains the standard osmotic agent although amino
  3. 3. 1084 TEITELBAUM AND BURKART acids and polyglucose are available for clinical dothelial cells by diffusion, polyglucose is slowly use in most countries. absorbed through lymphatics. Thus, it can main- ● Glucose. Standard dialysis solutions contain tain its colloid osmotic force over long dwells of glucose as the osmotic agent. Glucose has up to 18 hours. Furthermore, the rate of absorp- been shown to be safe, effective, readily tion is not influenced by peritoneal transport metabolized, and inexpensive. However, glu- type, as is the absorption rate of glucose by cose is not an “ideal” osmotic agent because diffusion. The safety of icodextrin use has been of the following properties or effects: rapid established. Reported side effects include skin absorption; the potential for metabolic de- rash and sterile peritonitis. Indications for the use rangements (such as hyperglycemia, hyper- of polyglucose include the long dwell of CAPD insulinemia, hyperlipidemia, and obesity); (overnight); the daytime dwell of continuous the necessity for an acidic dialysis pH to cyclic PD (CCPD); patients with loss of ultrafil- prevent caramelization; and the potential tration (high transporters, patients with loss of nonenzymatic glycosylation of peritoneal aquaporins); during episodes of peritonitis; and tissue. Glucose solutions induce a crystal- loid osmotic gradient to drive ultrafiltration. in patients with diabetes mellitus (to decrease ● Amino Acids. There is an obligatory daily glucose load). loss of protein and amino acids into the ● Biocompatibility Issues. In a typical PD peritoneal effluent. Therefore, a potential patient, the peritoneal cavity is exposed to new advantage of amino acid–containing fluids dialysis fluids at least 4 times daily. These dialy- would be that the absorbed osmotic agent sis solutions exert biologically and chemically would be a non–phosphorous-containing induced effects not only on the peritoneal mem- protein caloric source and that the amino brane and mesothelial cell, but also on the resi- acids absorbed would replace or exceed the dent leukocytes, macrophages, and fibroblasts. obligatory amino acids lost in the effluent Peritoneal biopsies in patients on long-term PD on a daily basis. However, studies document- have revealed ultrastructural changes (eg, glyco- ing the long-term efficacy of amino acids as sylation of capillary proteins) possibly induced a nutritional supplement have been contro- in part by the dialysis solutions. Data suggest versial. Complications include the develop- that di(2-ethylhexyl)phthalate (DEHP), the most ment of metabolic acidosis and increased commonly used plasticizer for polyvinylchlo- levels of serum urea nitrogen. The use of ride, may have adverse effects on macrophage 1.1% amino acid solutions results in ultrafil- function. Furthermore, it has been shown that tration and solute clearance rates similar to glucose degradation products produced during those using 1.5% dextrose solutions. heat sterilization and storage of glucose contain- ● Polypeptides/Oligopeptides. Polymers of ing solutions participate in the nonenzymatic glucose (icodextrin or polyglucose) can in- cross-linking of proteins leading to the formation duce a colloid osmotic force to drive ultrafil- of advanced glycosylation end products (AGEs). tration. Whereas glucose induces transcapil- ● Conclusions. Although commercially avail- lary ultrafiltration across both small able dialysis solutions based on lactate and glu- interendothelial and ultrasmall transcellular pores (via crystalloid forces), glucose poly- cose have provided adequate treatment of end- mers induce ultrafiltration across interendo- stage renal disease for thousands of patients, they thelial pores and the relatively few large do alter mesothelial cell and peritoneal macro- pores (via colloid osmotic forces). Ultrafil- phage function. Furthermore, pathologic alter- tration with glucose is rapid and occurs ations of the peritoneal membrane that may be early in the dwell (due to large crystalloid related to components of the PD solutions have osmotic gradient) and decreases with time been described. Newer solutions that address as glucose is absorbed, whereas with poly- these needs have been developed and are in glucose, ultrafiltration is constant but slow. clinical use. However, the long-term outcomes/ In contrast to glucose-containing solutions, benefits of such solutions for the patient are not where the glucose is absorbed via small interen- yet fully understood.
  4. 4. CORE CURRICULUM IN NEPHROLOGY 1085 Peritoneal Membrane bers, blood vessels, the lymphatics, occa- ● Anatomy sional macrophages, glycosaminoglycans, and fibroblasts. There are aqueous and li- The peritoneal membrane is the primary inter- pophilic phases. The aqueous phase medi- face between the blood and the dialysate compart- ates transport of water, electrolytes, protein, ments. This membrane is composed of 2 princi- nutrients, and hormones. pal parts: (1) the parietal peritoneum (about 10% ● Blood Vessels. Total splanchnic blood flow of total), which covers the inner surface of the in normal adult humans at rest ranges from abdominal and pelvic walls including the dia- 1,000 to 2,400 mL/min. The blood supply to phragm; and (2) the visceral peritoneum (about the visceral and parietal membranes arises 90% of total), which covers the visceral organs from 2 sources: (1) the celiac and mesen- including the intra-abdominal portion of the gas- teric arteries, with venous drainage via the trointestinal tract, liver, and spleen, and forms portal vein; and (2) the circumflex, iliac, the omentum and the visceral mesentery, where lumbar, intercostal, and epigastric arteries it reflects over and connects the loops of bowel. draining directly into the systemic circula- The total surface area of the peritoneal mem- tion, bypassing the hepatic portal system. brane (parietal and visceral) is thought to approxi- The number of perfused capillaries deter- mate the body surface area in most adults (ie, 1 to mines the so-called “effective peritoneal sur- 2 m2). Children have a disproportionately larger face area,” ie, functional area for exchange peritoneal surface area than most adults. The between blood and dialysate. The capillary peritoneal cavity usually contains about 100 mL walls are believed to contain at least 2 of fluid or less; however, a normal-sized adult distinct pore sizes, with the larger pores can usually tolerate 2 L or more without discom- located primarily at the venular end and the fort or compromise of pulmonary function. From smaller pores at the arteriolar end. Endothe- the perspective of PD, important anatomic com- lial cells also appear to have intracellular ponents of the peritoneal membrane include the pores or channels thought to be aquapores. mesothelial cells, an underlying basement mem- ● Peritoneal Lymphatics. As in most body brane, the interstitium, the microcirculation, and tissue, there is a network of lymphatic ves- the visceral lymphatics. sels that aid in removal of fluids and solutes ● Mesothelium. The mesothelium is a continu- from the interstitium. The fluid absorption ous monolayer of cells ultrastructurally simi- occurs primarily through stomata in the sub- lar to type II pneumocytes found in the diaphragmatic area. Many physiologic fac- pulmonary alveoli. These cells secrete sur- tors notably alter the rate of lymphatic up- factant-like lubrication for the peritoneum, take, and these include intraperitoneal are active in modulating host defense, and hydrostatic pressure, body posture, and phar- have been shown to produce cancer antigen macologic agents. (CA) 125. The CA125 appearance rates in the dialysate effluent may be used to esti- ANATOMIC FINDINGS IN PD PATIENTS mate mesothelial cell mass and possibly the Clinical observations by surgeons experienced effect of changing to more “biocompatible” with CAPD patients suggest that the peritoneal solutions on overall peritoneal membrane surface develops a diffuse opacification at times health. with local accentuation, which can progress to ● Basement Membrane. A homogenous base- the “tanned” peritoneal syndrome or, in ad- ment membrane underlies the mesothelial vanced stages, to sclerosing encapsulating perito- cells, is between 25 and 40 mm thick, and is neal fibrosis. In most patients, these changes are believed to be composed of type IV colla- minimal, even in those who have been on PD for gen, proteoglycogens, and glycoproteins. up to 10 years. The hypothesis is that chronic ● Interstitium. The interstitium is the support- uremia is associated with high levels of circulat- ing structure of the peritoneum and is com- ing reactive carbonyl compounds (RCCs), which posed primarily of a mucopolysaccharide initiate AGE formation in the peritoneum. Dur- matrix. It contains bundles of collagen fi- ing PD, RCCs contained in glucose-containing
  5. 5. 1086 TEITELBAUM AND BURKART solutions (as a result of the sterilization process) the capillaries and the interstitium, and that will amplify AGE formation. The RCCs and the blood phase is distributed within the AGEs initiate a number of cellular responses peritoneal interstitium. This model includes including vascular endothelial growth factor, the theory that the distance between capil- which interacts with endothelial cells stimulating lary and mesothelial surface, as well as angiogenesis and increasing vascular permeabil- number of capillaries, influence transport. ity. Use of more biocompatible solutions my ● “Three-pore” model, yields the most realis- slow or prevent this process. tic estimations of small-solute reflection co- efficients, macromolecule transfer, and the PERITONEUM AS A DIALYSIS SYSTEM effects of lymphatic absorption and ultrafil- ● Resistance to Salt and Water Transport. tration profiles observed clinically even The barrier for mass transport appears to when high-molecular-weight solutes are used offer very little resistance to solute trans- as osmotic agents. port by diffusion but seems to offer signifi- cant resistance to solute transport by convec- PHYSIOLOGY OF PERITONEAL TRANSPORT tion. The clinical significance of this is that ● Solute Transport by Diffusion solute removed by convection is not re- ● Diffusion, defined as a tendency for solutes moved at the same concentration as it is in to disperse themselves within the space plasma. There is more resistance to flow for available, is the most important mechanism these solutes than there is for water. This is responsible for solute transport into the peri- especially true when ultrafiltration is driven toneum. In PD, the diffusive clearance of by small osmotic solutes, “crystalloid osmo- any solute depends on the “effective” perito- sis,” but it is less significant when ultrafiltra- neal membrane surface area, the intrinsic tion is driven by hydraulic pressure or col- permeability of the membrane, dialysate loid osmosis. An example of this is sodium flow, concentration gradients, and time al- “sieving” and the observation that, early in lowed for transport. Overall solute clear- the dwell with a glucose-containing solu- ance can never exceed the lowest of these tion, dialysate sodium decreases. parameters. Typical dialysate flow rates are The interstitium represents the longest dis- markedly lower than those of capillary blood tance that solutes must traverse. There is increas- flow or membrane transport capabilities. ing evidence to suggest that the interstitium is Standard PD therapies are therefore limited one of the major resistance sites for urea and low by dialysate flow. molecular weight solute transport. The intersti- Diffusion becomes more restricted as molecu- tium is thought to be represented by a 2-phase lar weight increases (ie, urea diffuses faster than system that contains a gelatinous mucopolysac- creatinine). In fact, in contrast to what is ob- charide matrix interspersed with a water-rich, served for small solute clearance where increas- colloid-poor, free-fluid phase containing aque- ing number of exchanges per day tends to in- ous channels. crease daily clearance even if already during 24 ● Models of Peritoneal Transport hours of dwell, once on 24 hours/day of dwell Despite the complexity, investigators have at- time, further increases in the number of ex- tempted to characterize peritoneal membrane changes/day does not increase middle molecule transport properties in terms of classical mem- clearances. brane physiology using mathematic models. ● Ultrafiltration: Net ultrafiltration is achieved These models can help the nephrologist under- clinically by creating an osmotic pressure stand peritoneal solute and water transport and gradient (crystalloid or colloid) between guide in individualizing prescriptions for pa- blood and dialysate. Historically, dialysis tients. fluids achieved this via crystalloid osmosis ● “Distributed” models of peritoneal transport by adding various concentrations of glucose assume that the barrier separating blood to the solutions. Newer fluids use polyglu- from dialysate is not homogeneous but is cose to induce colloid-driven ultrafiltration. composed of distinct elements, including Solutes present in body fluids can be swept
  6. 6. CORE CURRICULUM IN NEPHROLOGY 1087 along with the bulk solvent flow even in the vents. This is most commonly observed absence of a concentration difference for net during dwells with solutions containing glu- diffusion, contributing to overall solute clear- cose as the osmotic agent and is mainly due ance. This contribution to net solute clear- to water movement across transcellular aqua- ance has been termed “solvent drag” or porins. The most important clinical conse- “convection.” quences are those related to the transport of ● Kinetics of Peritoneal Ultrafiltration: In Na . These expected changes in dialysate addition to ultrafiltration, absorption of Na concentrations during the dwell can be fluid from the peritoneal cavity also occurs. helpful in evaluating a patient with loss of This is mainly due to absorption of fluid ultrafiltration. If a patient is on automated through the tissues of the anterior abdomi- therapy and there is aggressive overnight nal wall and by the peritoneal lymphatics. ultrafiltration, there may be relatively more Intraperitoneal volume at any time is water than sodium removal. therefore determined by the relative mag- ● Lymphatic Absorption: Intraperitoneal fluid nitudes of transcapillary ultrafiltration and is continuously absorbed from the perito- anterior wall plus lymphatic absorption. neal cavity. The fluid can either be absorbed Polymers of glucose (icodextrin or directly into the subdiaphragmatic perito- polyglucose) can induce a colloid os- neal lymphatics or through the interstitial motic force to drive ultrafiltration. tissue of the peritoneal membrane. Hydrau- Whereas glucose induces transcapillary lic pressure effects when standing or when ultrafiltration across both small interendo- associated with activity may alter the rela- thelial and ultrasmall transcellular pores/ tive amount of convective movement of aquaporins (via crystalloid forces), glu- fluids and solute into the subdiaphragmatic cose polymers only induce ultrafiltration or other lymphatics. Data suggest that in- creases in intraperitoneal pressure are asso- across interendothelial pores (via colloid ciated with an increase in lymphatic absorp- osmotic forces). Ultrafiltration with glu- tion rates. Measurements of lymphatic cose is rapid and occurs early in the dwell absorption rates in CAPD patients using (due to large crystalloid osmotic gradient) intraperitoneal dextran as a marker ranged and decreases with time as glucose is from 0.1 to 3.5 mL/min with a median value absorbed, whereas with polyglucose, ultra- of 1.0 ml/min or about 2.2 L/day. filtration is constant but slow. Thus, for 2-L solutions containing 1.5% dextrose (1.36% glucose), osmotic equi- CLINICAL OBSERVATIONS OF PERITONEAL librium and maximal drain volume are MEMBRANE FUNCTION reached after about 2 hours of dwell time Characterization of Peritoneal Membrane in most patients, whereas peak intraperito- Transport: In the presence of infinite peritoneal neal volumes are not likely to occur until capillary blood and dialysate flows, solute clear- after a 3- or 4-hour dwell with 4.25% ance is directly proportional to peritoneal surface dextrose (3.86% glucose). area and indirectly proportional to overall resis- ● Solute Transport by Convection: Solutes tance. A measurement of clearance under these present in body fluids can be swept along conditions is a measurement of the intrinsic with the bulk flow of water during ultrafiltra- transport properties of the peritoneal membrane. tion even in the absence of a concentration Ideally, these measurements are primarily a func- gradient for net diffusion. This solvent drag tion of peritoneal diffusive permeability (cm/ or “convective solute” transport does not min) and effective surface membrane area (in occur in amounts per liter of ultrafiltrate cm2). Measurements of mass transfer area coeffi- equal to the physiologic concentration of cients (MTACs) are thought to approximate this solutes in body fluids. In other words, there state. However, as MTAC measurements are is a sieving effect that depends on resistance relatively complex, the simpler peritoneal equili- forces intrinsic to the membrane and sol- bration test (PET) has become the standard tool
  7. 7. 1088 TEITELBAUM AND BURKART Fig 1. Peritoneal equilibration test. Reprinted with permission.20 used clinically to characterize peritoneal mem- As seen in Fig 1, peritoneal membrane trans- brane transport. The protocol for the standard port is divided into 4 categories: high, high PET is as follows: average, low average, and low. Patients who 1. The test is performed in the morning after exhibit high membrane transport (lightest quar- complete drain of the prior long ( 8 hours) tile) will most rapidly equilibrate creatinine (and dwell. urea) and achieve excellent solute clearance. 2. Using 2.5% dextrose dialysate, the pa- However, they also rapidly absorb glucose from tient’s usual fill volume is infused. the peritoneal cavity, thereby dissipating the os- 3. A sample of dialysate for determination of motic gradient favoring ultrafiltration. There- creatinine, urea, and glucose is taken imme- fore, they have low drain volumes and will often, diately after infusion and at 2 and 4 hours. in fact, reabsorb fluid from the peritoneal cavity 4. A blood sample for determination of creati- during long dwells. These patients will often nine, urea, and glucose is taken 2 hours benefit from performing CCPD with more fre- after infusion. quent exchanges and shorter dwell times. They 5. The dialysate is drained after 4 hours, and may also benefit from the use of icodextrin the drain volume is recorded. during their long day dwell. Conversely, patients 6. The dialysate to plasma (D/P) ratios for who exhibit slow membrane transport (darkest creatinine and urea and the ratio of glucose quartile) have poorer solute clearance. There- in the dialysate compared to its initial con- fore, these patients may benefit from longer centration (D/D0) at times 2 and 4 hours are dwell times (CAPD) and larger exchange vol- calculated and plotted on the standard PET umes. However, because they dissipate their os- graph (Fig 1). motic gradient slowly as well, these patients
  8. 8. CORE CURRICULUM IN NEPHROLOGY 1089 ultrafilter very well. Patients in the 2 average ● Peritoneal Dialysis Modalities groups tend to do well with both solute clearance ● CAPD. Typically patients perform 4 manual and ultrafiltration. exchanges/day. A newer modification of Stability of Peritoneal Membrane Over Time: CAPD incorporates 1 nighttime exchange Longitudinal observations in CAPD patients sug- with a simple nightly exchange device; that gest that most patients have no significant change is, the patient receives a total of 5 exchanges/ in small solute clearance over time. If anything, day, with 2 overnight exchanges and 3 ex- there tends to be an increase in vascularity result- changes during the day. ing in an increase in the D/P ratio of small ● Cycler Dialysis. Patients on CCPD will typi- solutes. It should be noted, however, that D/P cally program the cycler to perform mul- ratios are influenced by instilled volume, rate of tiple automated exchanges overnight. Most diffusion, net ultrafiltration, and solute transport then perform a last bag fill; that is, the by convection. Therefore, a change in a D/P machine will deliver a dialysate exchange at value does not necessarily indicate that the pa- the end of the nighttime cycler dialysis. tient’s MTAC, ie, intrinsic membrane permeabil- A minority of patients will perform cycler ity, has actually changed. dialysis overnight and not perform a last bag fill. Thus, these patients have a dry day; they CHOICE OF DIALYSIS MODALITY do not carry any dialysate in their peritoneal cavity during the day. Potential indications of PD include patients ● Tidal Peritoneal Dialysis (TPD). TPD con- who have problematic vascular access, or who sists of the repeated instillation of small prefer home dialysis but cannot perform home tidal volumes of dialysis fluids with the use hemodialysis due to a lack of a partner or suit- of an automated cycler. There is little evi- able home environment. Absolute contraindica- dence to suggest that TPD can provide clear- tions to PD include a documented loss of perito- ances that are superior to that provided by neal function or extensive abdominal adhesions cycler dialysis. that limit dialysate flow. Under these conditions, it will not be possible to achieve an adequate ADEQUACY OF PERITONEAL DIALYSIS dose of dialysis. There are a number of relative contraindica- The National Kidney Foundation (NKF)/ tions to PD. Body size limitations are probably DOQI clinical practice guidelines, first published the most common cause. When anuric, it is in 1997 and subsequently revised in 2000, pro- difficult, but not impossible, to achieve current vide evidence-based guidelines for the provision Kidney Disease Outcomes Quality Initiative (K/ of adequate PD. These guidelines provide recom- DOQI) targets for adequate dialysis in patients mendations about when to initiate dialysis, how who weigh more than 100 kg. Other relative and when to measure PD dose, and recommenda- contraindications include patients with bowel tions for an adequate dose of dialysis. pathology, specifically diverticulitis, ischemic ● Measurement of Peritoneal Dialysis Dose: bowel disease, or inflammatory bowel disease; Solute clearance occurs by both residual abdominal wall or skin infections increase the renal and peritoneal removal of solutes. risk of catheter exit-site infection and thus in- Thus, when measuring total solute clear- crease the risk for peritonitis. Although, there are ance, both volumes should be collected. reports of doing PD in some patients who have One currently uses weekly Kt/Vurea and either an ileostomy or a colostomy, an abdominal total weekly creatinine clearance normal- prosthesis should be in place for a minimum of 6 ized to 1.73 m2 body surface area (BSA). weeks, and sometimes as long as 16 weeks, to This testing should be done more fre- allow sufficient time for complete healing prior quently if there has been either a significant to initiating PD. Although the presence an ab- change in clinical status or if there has been dominal aortic prosthetic graft is not a contraindi- a change in the PD prescription. One could cation to PD, there is limited clinical experience target PD dose by ignoring the residual in this area. renal component in their calculations, rely-
  9. 9. 1090 TEITELBAUM AND BURKART ing on peritoneal clearance alone if indi- renal function was similar in the 2 groups. Pa- cated. If residual renal clearances are in- tient survival was similar in the interventional cluded, the calculations for Kt/Vurea are and standard groups, even after adjustment for obtained using urea clearance, while one comorbid conditions such as age, presence of uses an estimation of glomerular filtration diabetes mellitus, serum albumin levels, anuria, rate (the mean of the urea and creatinine and normalized protein equivalent of total nitro- clearances) for the weekly creatinine clear- gen appearance. As a result, guidelines for ad- ance measure. equacy of PD are likely to be revised. ● Adequate Dose of Peritoneal Dialysis: Based on the results of many clinical stud- WRITING THE DIALYSIS PRESCRIPTION ies performed during the past 10 years, the ● Initial Prescription: The PD prescription NKF/DOQI workgroup has developed can be developed either empirically or guidelines for an adequate dose of dialysis. through the use of a computer-modeling For CAPD patients, the delivered PD dose program using data based on the patient’s for Kt/Vurea should be at least 2.0. The weight, residual renal function, and any recommended weekly creatinine clearance lifestyle constraints that may be present. dose is based on the patient’s transport ● Adjustments to the Initial Dialysis Prescrip- characteristics. For patients who are high or tion: Two to 4 weeks following the initia- high average transporters, the total creati- tion of PD, 24-hour collections of urine and nine clearance should be at least 60 L/wk/ dialysate should be performed, along with 1.73 m2. For patients who are low or low serum chemistries and a complete blood average transporters, the weekly creatinine count, in order to calculate the weekly Kt/ clearance should be at least 50 L/wk/1.7 Vurea and creatinine clearance. The initial m2. The dosage recommendations for auto- PET should be performed approximately 1 mated techniques are based on whether the month after the initiation of dialysis. This patient also has daytime exchanges. For waiting period is recommended as the PET patients using the cycler who have a dry results can change during the first month of day, the total Kt/Vurea should be at least 2.2 dialysis. The PET is performed to rule out and the weekly total creatinine clearance unexpected problems and also to identify should be at least 66 L/wk/1.73 m2. For patients who are either high or low transport- patients using the cycler who have at least 1 ers. High transporters will likely need short daytime dwell, the total Kt/Vurea should be dwell prescriptions and may develop ultra- at least 2.1 and the total weekly creatinine filtration problems as residual kidney func- clearance should be at least 63 L/wk/1.73 tion fails. Low transporters usually require m2. In malnourished patients, the estimate high dose CAPD or CCPD in order to of body size is adjusted up to ideal body maintain adequate dialysis as residual renal weight. Thus, for Kt/V urea, the target dose function decreases. If clearances are at or is increased by the ratio Vdesired/Vactual, while above target, then monitor adequacy at regu- for creatinine clearance the target dose is lar intervals as noted in the section measure- increased by the ratio BSAdesired/BSAactual. ment of PD dose above. If clearances are After the last PD guidelines were revised by below target, then modify the prescription the NKF/DOQI workgroup, the ADEquacy of and repeat adequacy testing. PD in MEXico (ADEMEX) trial was published. ● Further Adjustments to the Dialysis Pre- A total of 965 subjects were randomized to either scription: For CAPD patients, there are 2 standard care, where patients continued on their methods that can be used to increase dialy- present PD prescriptions, or to an interventional sis adequacy. The most common approach group, in which the dialysis prescriptions were is to increase the dwell volume/exchange. modified to achieve a peritoneal creatinine clear- One could also increase the number of ance of 60 L/wk/1.73 m2. The mean separation in exchanges/day. Alternatively, a nocturnal peritoneal creatinine clearances in the 2 groups exchange device is available that provides was approximately 10 L/wk/1.73 m2. Residual an extra exchange overnight, thus provid-
  10. 10. CORE CURRICULUM IN NEPHROLOGY 1091 ing the patient with a total of 5 exchanges ides, juxtaperitoneal infection, malignancy, or per day. For cycler patients, there are sev- allergic reactions should be considered. eral methods available for improving ad- ● Microbiology equacy. These methods include increasing Sixty to seventy percent of episodes are due to the dwell volume/exchange, increasing the Gram-positive cocci, most commonly Staphylo- time spent overnight on the cycler, increas- coccus aureus or epidermidis. Gram-negative ing the number of exchanges on the cycler, rods account for 15% to 25% and fungi for 2% to or increasing the number of daytime dwells. 3%. In approximately 15% of episodes, no organ- Sometimes a combination of the above mea- ism is cultured. Tuberculosis is a rare cause of sures is used in an individual patient. peritonitis in the United States. The finding of anaerobic and/or polymicrobial COMPLICATIONS OF PERITONEAL DIALYSIS peritonitis should raise the question of an intraab- dominal catastrophe and prompt a surgical evalu- Patients performing PD may experience either ation. When due to pancreatitis or a ruptured infectious or noninfectious complications. viscus, peritonitis may be associated with an elevated amylase ( 50 IU/L) in the dialysate. ● Infectious Complications ● Treatment Infectious complications account for approxi- Send dialysate for cell count with differential mately two thirds of all PD catheter losses and and Gram stain. Initiate therapy guided by Gram around one third of all transfers to hemodialysis. stain results. The major infectious complications of PD are The International Society for Peritoneal Dialy- peritonitis and exit-site or tunnel infections. sis (ISPD) recommendations for the initial/ ● Peritonitis empiric therapy of peritonitis have changed over The most common infectious complication of the years. The current recommendations are: PD. ● A significant cause of hospitalization, cath- Gram Stain Results Therapy eter loss, malnutrition, peritoneal mem- brane failure, and occasionally death. Gram-positive First-generation cephalosporin ● Average frequency approximately 1 episode Gram-negative Third-generation cephalosporin per 20 to 30 patient-months. The use of (an aminoglycoside may be disconnect systems has played a major used for patients with residual urine output role in lowering this frequency from the 100 cc/d) prior rate of 1 episode per 6 to 18 patient- No organism seen Combination of above agents months. ● Diagnosed when at least 2 of the following The use of vancomycin remains controversial. are present: The ISPD no longer recommends routine use of vancomycin for fear of inducing vancomycin resis- Cloudy dialysis effluent with white blood tance in enterococci. However, other authors still cell count 100 cells/mm3 (usually prefer it because of the high frequency of methi- 50% are polymorphonuclear neutro- cillin-resistant, coagulase-negative staphylococci. phils)—present in 98% of cases Attempts at treating fungal peritonitis with Abdominal pain—present in approximately amphotericin or a combination of fluconazole 75% of cases and flucytosine virtually always fail. Catheter Positive culture from dialysate removal should be considered very early. Other symptoms such as fever, nausea, or Final therapy should be guided by culture diarrhea are present in no more than half of results and sensitivities. Treatment should be all cases. continued for a total course of 2 weeks; infec- Not all instances of cloudy peritoneal dialy- tions due to S aureus, anaerobes, members of the sate reflect infectious peritonitis. Depending on Pseudomonas/Stenotrophomonas family, or those the cellularity of the fluid and the nature of the due to multiple Gram-negative organisms re- cells found, other causes such as fibrin, triglycer- quire 3 weeks of antibiotic therapy.
  11. 11. 1092 TEITELBAUM AND BURKART ● Relapsing Peritonitis: offending organism is a member of the Pseudo- Recurrence of peritonitis with the same organ- monas/Stenotrophomonas family, fungus, or my- ism within 4 weeks of the completion of therapy cobacterium. signifies relapse. ● Exit-Site Infection The recommended treatment for relapsing peri- • Defined by the presence of purulent drain- tonitis is: age with or without cutaneous erythema at the catheter-epidermal interface. Organism Therapy • Incidence ranges from 0.05 to 1.0 per patient- Gram-positive First-generation cephalosporin year. rifampin for 4 wk (use • Results in peritonitis in 25% to 50% of cases vancomycin or clindamycin and contributes significantly to catheter loss. in case of methicillin- • Trauma to the exit-site, an upward-directed resistance, ampicillin and an aminoglycoside for exit-site, or proximity of the distal catheter enterococcus) cuff to the exit-site ( 2 cm) all predispose Gram-negative to exit-site infection. Pseudomonas/ Remove catheter • The bacteriology of exit-site infections is Stenotrophomonas Other Third-generation cephalosporin very similar to that of peritonitis. (an aminoglycoside may be • Treatment: used for patients with residual urine output Send exit-site drainage for culture and Gram 100 cc/d) stain. Current recommendations for initial/ em- Relapsing peritonitis due to S aureus should piric therapy: prompt consideration of an occult tunnel infec- tion (Vida infra). Gram Stain Results Therapy Relapsing peritonitis due to Gram-negative organisms (or Gram-positives that fail to respond Gram-positive First-generation cephalosporin, after 96 hours of therapy) should prompt consid- trimethoprim/ eration of an intra-abdominal abscess. Ultra- sulfamethoxazole, or sonography or computed tomographic scanning penicillinase-resistant of the abdomen with intraperitoneal contrast may penicillin Gram-negative Oral quinolone be useful in establishing the diagnosis. Strong No organism seen Gram-positive coverage only consideration should be given to surgical explo- ration and catheter removal. It may be necessary to add rifampin for recal- Another potential concern when faced with citrant Gram-positive infections or a second relapsing peritonitis, especially when due to co- Gram-negative agent for infections with Pseudo- agulase-negative staphylococci, is the presence monas. of bacterial biofilm (so-called “slime”) on the Topical antibiotic therapy is not recommended. catheter. Intraperitoneal instillation of thrombo- However, the frequency of routine exit-site care lytic agents will sometimes prove successful in should be increased to twice daily. Application of eradicating the infection. dressings soaked in 3% saline or povidone- When catheter removal is necessary, it is gen- iodine solution may be beneficial. erally wise to wait 3 weeks or longer before Prolonged treatment (4 to 6 weeks) may be placing a new catheter as removal of the foreign necessary. Failure to eradicate the infection by body is often beneficial in promoting resolution that time should prompt consideration of catheter of infection. However, it is sometimes possible removal. Simultaneous catheter replacement at a to place the new catheter simultaneously pro- remote site is usually successful with the exception vided the white blood cell count of the dialysate of infections due to Candida or Pseudomonas. has decreased to 100/mm3. This should not be The frequency of exit-site infections and peri- done for relapsing peritonitis due to known or tonitis, particularly those episodes due to S au- suspected intra-abdominal abscess or when the reus, is approximately 4- to 7-fold higher in
  12. 12. CORE CURRICULUM IN NEPHROLOGY 1093 patients who are nasal carriers of S aureus. Prophy- • Failure of the PD catheter during infusion lactic treatment of PD patients with oral rifampin or may reflect intraluminal obstruction by fi- with mupirocin administered either intranasally or brin or clot. Flushing the catheter with hepa- topically at the exit-site have all been shown to rinized saline may be beneficial. Thrombo- markedly reduce the frequency of both exit-site lytic therapy is often needed. infections and peritonitis. Controversy remains • Distended loops of bowel due to constipa- as to whether all patients or only documented tion will often impair catheter outflow by carriers should be treated in this fashion. occluding many of the holes on the distal ● Tunnel Infection end of the PD catheter. This should always ● Defined by the presence of erythema, edema, be considered as the first possible etiology and/or tenderness over the subcutaneous for outflow obstruction and should be ad- catheter pathway associated with sangui- dressed with appropriate laxative therapy. nous, purulent, or thick drainage either spon- • Catheter obstruction may also be due to any taneously or when pressure is applied to the of a variety of other causes including: catheter tunnel. Adhesions due to prior peritonitis or sur- ● A loculated abscess involving the tunnel gery may cause the catheter to be trapped in may present with pain or signs of inflamma- a loculated compartment. Surgical lysis or tion without discharge. Ultrasonography of catheter repositioning/replacement may be the tunnel may be helpful in establishing the necessary. diagnosis. Catheters with the distal tip in the abdo- ● Tunnel infections are commonly associated men rather than the pelvis may be subject to with simultaneous exit-site infection with wrapping by active omentum (which does the same organism; when this is the case the not commonly extend into the pelvis). In risk of peritonitis is increased. this circumstance inflow of dialysate is usu- Treatment of tunnel infections is very ally not affected, as the pressure of the infusing dialysate will displace the offend- difficult. Antibiotic therapy is often unsuc- ing “flap” of omentum. Omental wrapping cessful. Irrigation of the tract with saline or most commonly presents within the first few a povidone-iodine solution is rarely benefi- months of initiating PD and is generally cial. When due to Gram-positive organisms painless. Omentectomy is often necessary. it may be possible to successfully treat the Peritonitis, particularly that due to fungi, infection by deroofing a portion of the cath- may present with catheter obstruction. eter tunnel; this technique is not successful ● Malposition for Gram-negative infections. Catheter re- • Though occasionally due to inappropriate moval and replacement is frequently neces- catheter placement at the time of insertion, sary; this may sometimes be accomplished malposition of the PD catheter is more com- successfully in a single operation as de- monly due to migration of the catheter tip scribed earlier in the section on peritonitis. out of the pelvic gutter into the upper abdo- ● Noninfectious Complications men. This is often associated with discom- As is the case for hemodialysis, patients per- fort, localized by the patient to the site of the forming PD are subject to numerous complica- catheter. Malposition may also be a cause of tions affecting many organ systems. This portion poor catheter drainage, particularly in pa- of the curriculum, however, will be confined to a tients attempting to drain in the upright discussion of complications specific to the perfor- position. Changing position during drain (eg, mance of PD. lying on the right side for catheters in the ● Catheter Malfunction right upper quadrant) may provide relief. • Catheter tips that have migrated to the left ● Obstruction upper quadrant may spontaneously reposi- • PD catheters may exhibit obstruction during tion themselves secondary to the actions of either the infusion or drain phases of an peristalsis favoring downward movement of exchange. the catheter on the left side. In contrast,
  13. 13. 1094 TEITELBAUM AND BURKART spontaneous repositioning of a catheter that • Generalized Pain has migrated into the right upper quadrant is Patients performing PD may occasionally very unlikely as peristalsis favors continued experience pain in the lower back or shoulder. upward movement of the catheter on this side. Back Pain • When catheter malfunction due to migration is present and spontaneous repositioning Back pain may be due to either alter- does not occur, mechanical intervention is ations in posture induced by the presence of necessary. The catheter position may be cor- several liters of intraperitoneal fluid or due rected by intraluminal manipulation with a to the weight of the fluid itself. It may stiff guide wire, use of a Fogarty catheter, or respond to exercise training. Alternatively, a surgery (often laparoscopic). Some sur- change to APD with no or minimal daytime geons will suture the catheter to the dome of dwell volumes may be beneficial. the bladder or internal abdominal wall to Shoulder Pain “tack it” into place. ● Pain Shoulder pain may reflect irritation of the Patients performing PD may experience pain underside of the diaphragm due to the pres- associated with either the inflow or drain phases ence of either peritoneal dialysate or intra- of a PD exchange. Patients may also experience peritoneal free air. generalized pain bearing no direct temporal rela- May diminish when draining in Tren- tionship with the performance of an exchange. delenburg position. Usually resolves without specific treat- • Pain on Inflow ment. Commonly due to “jet” effect of dialysate ● Abdominal Fullness emerging from the distal end of the catheter at Many patients performing PD complain of a relatively high velocity, thereby irritating the sense of abdominal “fullness.” This becomes adjacent tissues. This is seen more frequently problematic when patients feel too full to eat. with straight catheters than in those with a This has long been thought to be simply a me- curled tip. chanical consequence of the presence of a large Also caused by the relatively low pH (5.2) volume of intraperitoneal fluid. However, the of the dialysate; exacerbated by increasingly magnitude of the symptoms have recently been hypertonic solutions. demonstrated to be proportional to the caloric May decrease with time on PD. content of the dialysate as patients do not experi- May diminish with the addition of lidocaine ence equally severe symptoms when carrying to solution bags prior to infusion. similar volumes of dialysate devoid of caloric Best treatment would be use of normal pH content (eg, polyethylene glycol). fluids; not currently available in the United ● Membrane-Related Complications States. • Ultrafiltration Failure • Pain on Outflow Please see the section on “Physiology of Unrelated to pH; rather, due to suction ef- Peritoneal Dialysis” for the diagnostic and fect on intra-abdominal viscera. therapeutic approaches to ultrafiltration failure. Commonly localizes to the rectal or supra- • Sclerosing Encapsulating Peritonitis (SEP) pubic areas. Usually worse in APD than CAPD and This is a rare but serious entity character- often positional. Usually worse toward end of ized by a thick-walled membranous “cocoon” drain. May reflect poor catheter position. encasing and entrapping loops of bowel. Pa- May resolve with time. If it fails to resolve, tients present with abdominal pain, nausea, pain may be lessened by incomplete drainage emesis, bowel obstruction (either small or (eg, tidal dialysis). Catheter repositioning or large), and ultrafiltration failure with poor sol- removal may be necessary. ute transport. The mortality rate is greater than
  14. 14. CORE CURRICULUM IN NEPHROLOGY 1095 50% despite medical and surgical treatment. comes manifest within the first month of initi- The etiology and pathogenesis of SEP are not ating PD; onset later than 1 year after the well understood. SEP may present years after initiation of PD is uncommon. Peritoneal dia- discontinuation of PD, even after renal trans- lysate transits the diaphragm either via lym- plantation. phatics or through congenital diaphragmatic ● Defects in Peritoneal Cavity Boundaries defects. Nearly 90% of cases occur on the right side. The reason for this is unclear; • Hernias and Abdominal Wall or Genital protection of the left hemidiaphragm by the Edema heart and pericardium has been postulated, as Due to the increase in intraabdominal pres- has a “piston” effect of the liver to propel sure associated with the performance of PD, dialysate across the right hemidiaphragm. hernia is a relatively common complication Patients most commonly present with pro- occurring in anywhere from 10% to 25% of all gressive dyspnea and/or orthopnea. Pain and PD patients. Hernias may be incisional (cath- acute onset of dyspnea are uncommon. eter site or other), ventral, umbilical, or ingui- Diagnosis—The pleural fluid is transuda- nal. It has been suggested that the frequency of tive and has a high glucose concentration. The hernias may be increased in females. cell count is variable. The diagnosis of Hernias often present with localized swell- PD-associated hydrothorax is confirmed by ing that is usually painless. In these instances demonstrating communication between the the diagnosis may be established via perito- peritoneal and pleural spaces. This may be neal scintigraphy or computed tomographic accomplished by injecting radiolabeled albu- peritoneography. It should be noted, however, min or technetium sulfur colloid into the peri- that intestinal obstruction due to strangulation toneal cavity and imaging the chest after allow- may occur in up to 10% to 15% of hernias, ing the patient to ambulate for an hour. particularly those at the catheter site or related to other abdominal incisions. Treatment—Patients may require thoracen- Dialysate leakage through congenital (eg, tesis for initial relief of symptoms. PD should patent processus vaginalis) or acquired (eg, be temporarily discontinued or, at a minimum, pericatheter or prior incisional site) abdominal changed to a modality associated with lower wall defects results in dissection of dialysate peak intraabdominal pressures, eg, lower vol- through soft tissue and fascial planes. This umes or nocturnal intermittent PD. Pleurode- will present with either genital (scrotal or sis with talc, triamcinolone, autologous blood, labial) edema or generalized swelling of the tetracycline derivatives, fibrin glue, or Nocar- abdominal wall and/or upper thigh, frequently dia rubra cytoskeleton may be attempted with a peau d’orange appearance. Ultrasound in case of recurrence. The procedure is or computed tomographic peritoneography are often poorly tolerated due to pleural irrita- usually diagnostic. The latter may be per- tion. Surgical repair via a limited thora- formed without radiocontrast, as the presence cotomy is indicated if pleurodesis fails. Al- of the dialysate itself may serve in this fashion ternatively, patients may elect to transfer to and allow for definition of the defect. hemodialysis. While dialysate leaks may occasionally ● Metabolic Abnormalities resolve after temporary cessation of PD or • Hypoalbuminemia a switch to nocturnal intermittent PD, surgi- cal repair is nearly always necessary. Ab- Patients performing PD lose approximately dominal hernias invariably require surgical 4 to 7 g of albumin per day across the perito- repair. neal membrane. Therefore, hypoalbuminemia is more commonly observed than in patients • Hydrothorax performing hemodialysis. Consequently, ef- Hydrothorax is a rare complication ( 2%) forts should be made to maintain the patients’ of PD. For unknown reasons there is a marked dietary protein intake 1.2 g/kg/d if at all female preponderance. It most commonly be- possible.
  15. 15. 1096 TEITELBAUM AND BURKART • Weight Gain, Hypertriglyceridemia, Hyper- 7. Mujais S, Vonesh E: Profiling of peritoneal ultrafiltra- glycemia tion. Kidney Int Suppl 62:S17-S22, 2002 8. Gokal R: Newer peritoneal dialysis solutions. Adv Ren More than half of all PD patients will expe- Replace Ther 7:302-309, 2000 9. Krediet RT, Zweers MM, Ho-dac-Pannekeet MM: The rience 1 or more of these problems that arise effect of various dialysis solutions on peritoneal membrane due to the increased caloric load provided by viability. Perit Dial Int 19:S257-S266, 1999 (suppl 2) the dialysate. A low-fat diet, increased activ- 10. Flessner MF: The role of extracellular matrix in ity, and strict adherence to fluid restriction, transperitoneal transport of water and solutes. Perit Dial Int thereby minimizing the need for hypertonic 21:S24-S29, 2001 (suppl 3) 11. Devuyst O: New insights in the molecular mecha- dialysate, will help attenuate these problems. nisms regulating peritoneal permeability. Nephrol Dial Trans- Use of the non–glucose-based dialysate, ico- plant 17:548-551, 2002 dextrin, as an alternative osmotic agent for the 12. Mujais S, Nolph KD, Gokal R, et al: Evaluation and long dwell may be beneficial as well. management of ultrafiltration problems in peritoneal dialy- sis. Perit Dial Int 20:S5-S21, 2000 (suppl 4) 13. Davies SJ, Phillips L, Naish PF, et al: Peritoneal REFERENCES glucose exposure and changes in membrane solute transport 1. US Renal Data System: USRDS 2002 Annual Data with time on peritoneal dialysis. J Am Soc Nephrol 12:1046- Report: Atlas of End-Stage Renal Disease in the United 1051, 2001 States. National Institutes of Health, National Institute of 14. NKF-K/DOQI Clinical Practice Guidelines for Perito- Diabetes and Digestive and Kidney Diseases. Bethesda, neal Dialysis Adequacy. New York, NY, National Kidney MD, 2002, pp 151-164 Foundation, 2000 2. Collins AJ, Hao W, Xia H, et al: Mortality risks of 15. Raj DSC, Choudhury D, Welbourne TC, et al: Ad- peritoneal dialysis and hemodialysis. Am J Kidney Dis vanced glycation end products: A nephrologist’s perspective. 34:1065-1074, 1999 Am J Kidney Dis 35:365-380, 2000 3. Paniagua R, Amato D, Vonesh E, et al: Effects of 16. Keane WF, Bailie GR, Boeschoten E, et al: Adult increased peritoneal clearances on mortality rates peritoneal peritoneal dialysis-related peritonitis treatment recommenda- dialysis: ADEMEX, a prospective, randomized, controlled tions: 2000 update. Perit Dial Int 20:396-411, 2000 trial. J Am Soc Nephrol 13:1307-1320, 2002 17. Rocklin MA, Teitelbaum I: Noninfectious causes of 4. Nolph KD, Hano JE, Teschan PE: Peritoneal sodium cloudy peritoneal dialysate. Semin Dial 14:37-40, 2001 transport during hypertonic peritoneal dialysis. Ann Intern 18. Teitelbaum I: Vancomycin for the initial therapy of Med 70:931-941, 1969 peritonitis: Don’t throw out the baby with the bath water. 5. Jones MR, Gehr T, Burkart JM, et al: Replacement of Perit Dial Int 21:235-238, 2001 amino acid and protein losses with 1.1% amino acid perito- 19. Gokal R, Alexander S, Ash S, et al: Peritoneal cath- neal dialysis solution. Perit Dial Int 18:210-216, 1998 eters and exit-site practices toward optimum peritoneal ac- 6. Wolfson M, Ogrinc FG, Mujais S: Review of clinical cess: 1998 update. Perit Dial Int 18:11-33, 1998 trial experience with icodextrin. Kidney Int Suppl 62:S46- 20. Twardowski ZJ, Nolph KD, Khanna R, et al: Perito- S52, 2002 neal equilibration test. Peritoneal Dial Bull 7:138-147, 1987