COMPLICATIONS OF DIALYSIS - PART 3 pdf

Peritoneal Membrane Failure 163 dialysate volume drained from the patient over the day. An alternative to the standard or short PET is the Standard Peritoneal Permeability Assessment (SPA) in- troduced by Krediet and coworkers (138). In its origi- nal form, it employed a 1.36% glucose exchange com- bined with instilled intraperitoneal dextran as a large molecular weight marker to calculate changes in peri- toneal volumes. The glucose concentration has been revised to 3.86% to provide data for sodium sieving in the same test (see below), and a net drainage volume of 400 mL or less indicated ultrafiltration failure (139). Otherwise it is technically similar to the standard PET, provided the same precautions are observed (Table 2). B. Measurement of Fluid Reabsorption (Relative Lymphatic Absorption) The estimation of fluid reabsorption from the peritoneal cavity, whether by lymphatics or capillaries due to the oncotic pressure difference between blood and dialy- sate, remains difficult and controversial. The method involves measuring the rate of disappearance of a mac- romolecular marker, e.g., dextran, and at present is a research rather than a clinical tool (138). However, there are clues that will suggest that it is a significant problem, e.g., patients whose net ultrafiltration on the PET test is consistently less than would be expected from the relationship described by the regression line in Fig. 6 (28). Equally, patients in whom the net reab- sorption of fluid following a long dwell is excessive are likely to have this problem. In both situations the likelihood of it contributing to peritoneal failure is in- creased if sodium sieving has been demonstrated to be normal. C. Assessing Intrinsic Peritoneal Permeability Measurement of intrinsic peritoneal permeability is complex and involves the estimation of the restriction coefficient of one or more macromolecules (24). As with estimates of lymphatic absorption, this remains a research tool, perhaps as a marker for interstitial fibro- sis. At present there is no evidence that either absolute or interpatient differences in intrinsic peritoneal per- meability influence clinical aspects of peritoneal function. D. Measurement of Sodium Sieving The purpose for measuring sodium sieving is twofold. First, it is helpful in the diagnosis of membrane failure (see below). Second, it will draw attention to the im- pact sodium sieving will have on the relative removal of salt and water from the patient. It is most easily measured by calculating the dialysate to plasma ratio of sodium one hour after the instillation of a hypertonic (3.86% glucose) exchange (22,139). A lower ratio (0.81–0.85) implies that sodium sieving occurs, whereas a higher ratio (0.87–0.94) indicates that this process has become much less efficient due to a clini- cally significant loss in the number of ultrasmall pores. Where possible, this test should include the measure- ment of the net ultrafiltration at 4 hours, where a value of less than 400 mL should raise concerns of ultrafil- tration failure (139). It has been suggested that this test be combined with the standard PET to reduce workload by utilizing a 3.86% rather than a 2.27% glucose exchange and the taking of a sample at one hour. The disadvantage of this approach is that many nephrolo- gists will have considerable historical data on their pa- tients using the standard PET method or alternatively use the short version of the PET, in which only the sample obtained at 4 hours is used. Under these cir- cumstances it is easy to proceed to a 3.86% exchange in selected patients. E. Ex Vivo Markers of Peritoneal Structural Changes One of the significant advantages that PD provides is access to dialysis effluent within which various param- eters can be assessed. Indeed measurements (of medi- ator levels and the cellular components) in drained ef- fluent have provided the basis for our understanding of the process of peritoneal inflammation in vivo (51,52,54–59,140). The ready access to this material has made it an attractive proposition within which to measure levels of markers that might be indicative of changes in the function of the membrane or its consti- tutive parts. In this respect, markers of mesothelial cell mass/turnover (CA125) (141–143), markers of endo- thelial cell function (factor VIII), and presumed fibrotic or wound-healing markers (pro-collagen I/III, hyalu- ronic acid, and TGF- ␤ 1) have been measured in PD patients at various points during treatment. Unfortu- nately, however, despite initial promise, particularly with CA125 as a mesothelial cell marker (and thus an indicator of mesothelial cell damage), the data provided so far have been cross-sectional and have produced conflicting results in different centers as to the rela- tionship between it and time on PD (142,144). There are only limited data correlating membrane functional changes with dialysate levels in CA125, and this is 164 Davies et al. Table 2 Comparison of Peritoneal Equilibration Test (PET) with Standard Peritoneal Permeability Analysis (SPA) Parameter PET SPA Dwell length 4 hours 4 hours Solution (glucose) 2.27% 1.36% or 3.86%* Solute transport characteristics D/P creat ratio at 4 hours (corrected for glucose). D/P creat and MTAC creat correlate well, although there is systematic error. For practical purposes the D/P creat is independent of glucose concentration, so values obtained using PET and SPA are interchangeable. Typical range of values: D/P creat 0.4–1.0. Mass transfer area coefficient (MTAC creat )orD/P ratio in simplified form of test. MTAC corrects for the convective component, and requires accurate measurement of intraperitoneal volumes before and after dwell (see below). Typical range of values: (MTAC creat 5.0–19.3 mL/ min/1.73 m 2 . Ultrafiltration Net UF volume at 4 hours. See Table 3 for values that are associated with clinical UF failure. Uses instilled dextran 70 (1 g/L) as a volume marker to establish residual volume, effective lymphatic absorption, and transcapillary ultrafiltration. In the simplified version a net UF volume of <400 mL using 3.86% exchange suggests UF failure. Sodium sieving This is not part of the routine PET and requires the use of a 3.86% exchange if done as part of the SPA. It can either be expressed as the simple D/P[Na ϩ ] at 1 hour (see Table 3) or be corrected for diffusion by subtracting the gradient of D/P[Na ϩ ] at 1 hour achieved with a 1.36% exchange from that achieved with 3.86% exchange. A corrected gradient of less than 5 mmol/L may indicate impaired transcellular water transport. There is, however, a relationship between solute transport status and Na ϩ sieving measured in this way, due to the more rapid loss of osmotic gradient in high transport patients. Intrinsic peritoneal permeability Not applicable. By measuring clearances of a number of proteins of varying sizes ( ␤ 2 -microglobulin), a restriction coefficient is calculated that equates to the intrinsic permeability. *Modified version of the test was a 3.86% exchange. mostly in patients with sclerosing peritonitis, where the complete loss of mesothelium is evidenced by low or undetectable CA125 levels (145). There is clearly a need for longitudinal studies on CA125 and other markers in individual patients to define the variability and thus the usefulness of these tests. Only when such data are available can definitive links between these markers and clinical changes in peritoneal function be established or refuted. IX. RECOGNITION OF PERITONEAL FAILURE A. Peritoneal Function and Solute Removal It is not the purpose of this chapter to define adequate solute removal for the PD patient, and the complica- tions related to inadequate delivery of dialysis dose are discussed elsewhere. However, peritoneal function does have an important influence on delivered dose primar- ily by influencing the net ultrafiltration achieved and thus the convective component to solute clearance. Difficulties are likely to be experienced in achieving adequate clearances in the anuric patient at either end of the solute transport spectrum. For patients with low solute transport, and thus a low effective peritoneal sur- face area it will be difficult to achieve targets (e.g. 60 liters creatinine clearance/week/1.73 m 2 ) in those with a large body surface area (146). When the PET was initially described this was considered potentially to be the principle limiting factor of peritoneal function. In practice, however, this has not turned out to be the case partially because it affects very few patients, (most large patients have D/P creatinine ratios of >0.6), but also because large patient size has not been found to be associated with adverse outcome in PD (39,147). In Peritoneal Membrane Failure 165 Table 3 Values from PET and Sodium Sieving Used to Define Ultrafiltration Failure A. Peritoneal equilibration test D/P creat at 4 hours Net UF volume (mL) High solute transport UF failure (see example A, Fig. 6) >0.85 <250 High effective lymphatic absorption (see example C, Fig. 6) <0.75 <150 Mixed type UF failure (see example B, Fig. 6) 0.75–08.5 <220 B. Sodium sieving test D/P [Naϩ] at 1 hour using 3.86% glucose exchange Impaired sodium sieving >0.87 fact there is increasing evidence that low solute trans- port patients do well on peritoneal dialysis. Neverthe- less, it remains an important consideration, and will have a greater impact if the chosen method of dialysis measurement is the creatinine rather than the urea clearance. For patients with high solute transport, the principle effect on achieved dialysis dose results from the rela- tively poor ultrafiltration achieved in these patients, and thus the reduced convective clearance. The differences between estimates of creatinine and urea clearances will be much more, and creatinine clearance targets will be easier to achieve in these patients. B. Peritoneal Function and Inadequate Fluid Removal—Ultrafiltration Failure It is in the area of fluid removal from the PD patient that assessment of peritoneal function is most impor- tant. Ultrafiltration failure may be defined from two standpoints: from the assessment of peritoneal function or from a clinical approach to the patient. The former may use a definition derived from peritoneal function testing, such as the failure to achieve more than 400 mL net fluid removal following a 4-hour hypertonic dialysate exchange (139) or less than 200 mL following a PET (see Table 3) (28). The latter would define ul- trafiltration failure as the inability to remove sufficient water (and salt, see below) to enable the patient to maintain their designated dry weight, while allowing an adequate fluid intake and avoiding dialysis regimes that result in excessive dialysate calorie intake and weight gain. This approach, while more clinically rel- evant, has the disadvantage of being less precise due to the difficulties in assessing true dry weight in PD patients and is confounded by other variables such as residual renal function and changing body composition. In practice, one will use a combination of both in the assessment of the patient. Patients with ultrafiltration failure have been found to have peritoneal function that differs from normal in three ways: they may have high effective peritoneal surface areas as measured by solute transport, high rel- ative lymphatic absorption rates resulting in reduced net fluid removal, or impaired transcellular water trans- port as evidenced by reduced sodium sieving (27,28,35,139). In the majority of such patients there is a combination of these problems, and the relative contribution of each factor is not always clear. A com- bination of the PET and sodium sieving test in most cases will give one sufficient information to diagnose the cause of the problem, and thus proceed to a rational approach to therapy. The diagnostic ranges of results obtained from the standard PET and sodium sieving tests are summarised in Table 3, which should be read in conjunction with Fig. 6 where sample patients have been plotted. It should be emphasized, however, that in assessing the patient with ultrafiltration failure that it is also useful to examine the total regime that the patient is using, with the results of net ultrafiltration achieved with each individual exchange as well as the total for a 24-hour period. It is difficult to imagine how an anuric PD pa- tient can sustain adequate nutrition on less than 1000 mL ultrafiltration per day, particularly in view of so- dium balance (see below), and it is likely that this should be a minimum target for such patients. Equally, it is important to know if any of the individual ex- changes result in the development of a positive balance, as this will result in a particular problem when trying to achieve target dry weights. 166 Davies et al. C. Problems of Electrolyte Balance Generally there are no problems associated with potas- sium removal in PD patients, for whom hyperkalaemia is rarely a problem. It is possible that with time and the development of malnutrition that PD patients be- come total body deficient in potassium, but this cannot be considered a direct result of membrane failure. In contrast, the removal of sodium from the anuric PD patient is critically dependent on ultrafiltration and thus peritoneal membrane function (148). This is best illustrated by an example calculation of an anuric pa- tient, with a plasma sodium concentration of 140 mmol/L, using dialysate containing 132 mmol/L, on a daily regime of 10 L. If no net ultrafiltration were achieved, then the maximum possible sodium removal per day, assuming complete equilibration with plasma, would be 80 mmol. In fact, due to the phenomenon of sodium sieving and incomplete equilibration during shorter dwells, this is likely to be an overestimate. Even allowing for gastrointestinal and sweat losses, this would not be sufficient to maintain balance. However, for every 100 mL of ultrafiltrate there is the potential to increase sodium removal by 10–14 mmol, depend- ing on the sodium sieving. Thus, both theoretically and empirically (148) the net sodium removed is very de- pendent on the ultrafiltration achieved. The actual val- ues obtained can easily be measured when assessing dialysis adequacy, and this should be done routinely in the anuric patient. It is also important to realize the impact of sodium sieving on the relative proportion of sodium to water removal in certain situations. For ex- ample, in patients having relatively high volume but short dwells with medium or high glucose concentra- tions, as may occur in patients on APD, ultrafiltration may appear adequate but sodium losses relatively low. This would be further exacerbated in the presence of dry days or net fluid absorption during the long daytime dwell period (149). D. Problems of Acid-Base Correction At present there are no firm data suggesting a trend to increasing acidosis in patients with deteriorating peri- toneal function in terms of solute or fluid removal. There are no studies reporting isolated problems with acid-base balance. In general the acid-base status of the patient is determined by the concentration of potential buffer, lactate, or bicarbonate in the dialysate (150). Stein et al. reported that patients’ nutrition is better if they are maintained with a dialysate containing a higher buffer concentration (40 mmol/L) as compared to a lower one (35 mmol/L) (151). E. Other Problems Associated with High Effective Peritoneal Surface Area In addition to the problems associated with peritoneal ultrafiltration, patients with high effective peritoneal surface areas are at additional risk for two other prob- lems: excessive peritoneal protein losses and increased dialysis calorie load, which may contribute to obesity. One of the undesirable systemic effects of peritoneal dialysis is the loss of plasma proteins into the dialysate, which can constitute between 5 and 15 g per day (152). The majority of the protein lost is in the form of al- bumin, and for reasons explained above albumin clear- ances are increased in high solute transport patients. This compounds the problem of hypoalbuminemia and edema in individuals who are already at risk of over- hydration from poor ultrafiltration further reduces plasma refilling. While co-morbidity and nutritional state remain important determinants of the plasma al- bumin, it is important to recognize that this problem is often due to peritoneal function. The absorption of glucose from the peritoneum is bimodal in the PD population (153), due to the syner- gistic effects of increased fractional absorption and higher dialysate glucose concentrations required by pa- tients with greater effective peritoneal surface areas. While this does not always lead to excessive fat gain and may in some cases provide a useful energy source (154), there is no doubt that in some patients this can lead to significant and problematic obesity. X. TREATMENT STRATEGIES FOR PERITONEAL FAILURE A. Peritoneal Function and Dialysis Prescription In prescribing peritoneal dialysis the principal aim is to use a regime that maximizes the total volume of dialysate drained from the patient. This is usually lim- ited first by the maximum volume that the patient can tolerate, which should and will be greater in larger pa- tients, and second by the patients’ peritoneal function. Table 4 shows the suggested possible regimes that can be used according to patient size and effective perito- neal surface area. The actual volumes used will depend upon the target of clearance required, the amount of residual renal function, and the volumes tolerated by the patient. Peritoneal Membrane Failure 167 Table 4 Potential PD Regimes According to Patient Size and Solute Transport Body surface area Effective peritoneal surface area (solute transport from PET) Low (D/P creat <0.5) Low-average (D/P creat 0.5–0.65) High-average (D/P creat 0.65–0.81) High (D/P creat >0.81) Small (<1.71) Use CAPD regimes with 21 dwells; if anuric may require extra exchanges; alter glucose according to solute transport. Use combination of short dwells, e.g., APD overnight with glucose polymer for long dwells. Medium (1.71–2.0) Large (>2.0) Use 2.5–3.1 exchanges, 5 or 6 per day, avoid short dwells and consider hemodialysis. Use CAPD regimes with dwell volumes according to patient size; larger anuric patients may require an extra dwell period during the night (CAPD patients) or the day (APD patients). Those with higher solute transport will require higher glucose concentrations. As patient size increases, use larger dwell volumes and add a further daytime dwell period. B. Strategies in the Management of Ultrafiltration Failure In designing a regime for the patient with clinical ev- idence of ultrafiltration failure, the first step is to es- tablish when, if at all, during the 24 hours the patient is developing positive fluid balance. Unless this is put right, the ability to achieve adequate fluid removal dur- ing the remainder of the day will be compromised. If this proves impossible using the strategies described, then it is likely that the patient will need to be switched to hemodialysis. Augmentation of residual urine vol- umes with diuretics may be considered, but this is un- likely to be a long-term solution. In addition to the standard range of glucose concen- trations available, there are now a variety of therapeutic procedures that can be adopted to improve ultrafiltra- tion, and a logical approach to their use is described in the algorithm (Fig. 7). These can be broadly divided into two categories: approaches that allow manipula- tion of dwell length and those that exploit alternative osmotic agents, although both may be combined into the same regime. The development of automated devices of increasing reliability has allowed one to manipulate the regime to a considerable degree. For example, a single long dwell in the daytime can be combined with four or five short dwells overnight using automated peritoneal dialysis. Alternatively, five equally spaced dwells throughout the 24-hour period may be used with an overnight assist device. In general terms, the patient with clinically rel- evant ultrafiltration failure will have little or no residual renal function, and thus the use of regimes that are dry either during the night or day are to be avoided in order to obtain adequate clearances. The most important development in the field of al- ternative osmotic agents has been the introduction of high molecular weight glucose polymers (Icodextrin) (155). This solution is able to create an oncotic pressure across the peritoneal membrane and achieve ultrafiltra- tion despite being iso-osmolar with plasma (156). It is ideally suited to improving ultrafiltration in patients with a high effective peritoneal surface area because it achieves most of its effects through the intercellular pores. It is important to recognize that the longer the dwell period, the better the ultrafiltration will be, at least up to 12 hours, e.g., in patients on APD (157). Original concerns regarding its safety appear to have been answered, although it is only licensed for use in one exchange per day (158). It may have particular advantages in reducing total calorie intake in patients in whom obesity is a problem or in situations where exposure of the peritoneum to glucose is being avoided. There is already evidence to suggest that its use may reverse some of the peritoneal changes associated with ultrafiltration, including reducing effective peritoneal surface area and enhancing transcellular water trans- port. 168 Davies et al. Fig. 7 Algorithm for the management options of ultrafiltration failure. Other nonglucose solutions include amino acids and glycerol, although the latter is not generally available. These have no specific role in ultrafiltration failure ex- cept as part of a glucose-free regime, which may allow peritoneal recovery. C. Improving Sodium Balance As indicated above, the best way to ensure that the patient has sufficient sodium removal is to establish adequate ultrafiltration (148). It is important to recog- nize, however, that in reality sodium does not fully equilibrate between plasma and dialysate, particularly in shorter dwells where higher glucose concentrations will result in excessive water removal—in effect due to the sieving of sodium. It is, therefore, necessary to measure the total sodium removal, particularly in edematous anuric patients, to establish the actual amount and match where possible to the dietary intake. Other approaches to this problem are currently being developed, in particular the use of dialysate solutions with a low sodium content (159,160). Sodium concen- trations ranging from 98 to 128 mmol/L have been as- sessed with conflicting results. Some have reported lit- Peritoneal Membrane Failure 169 tle value in the higher range but the development of concerning clinical symptoms (161), while others have found the ultra-low dialysate sodium solutions to be well tolerated and clinically efficacious (159,160,162). These differences are difficult to understand but may represent variability in dietary salt intake. D. Improving Acid-Base Balance As noted previously, acidosis has not been recognized as a feature of impaired peritoneal function. It is, how- ever, important to correct any tendency to a low plasma bicarbonate, and improvement has been shown to re- duce protein degradation and increase nutrition (163). Malnutrition is an important adverse risk factor for sur- vival during PD, and any measure that will prevent the occurrence of protein calorie depletion should be im- plemented. At present it appears that either 40 mmol/ L lactate or bicarbonate dialysate are better than lower concentrations of these ions at improving plasma bi- carbonate concentrations. In addition, mmol for mmol they appear to be equipotent. In addition, patient nu- trition appears to be better when using a 40 mmol/L concentration (151). The question of whether bicarbon- ate dialysate should be used because of enhanced bio- compatibility profile will be considered later. E. Enhancing Biocompatibility of Peritoneal Dialysis At this point it must be reemphasised that the vast ma- jority of evidence for PDF ‘‘bioincompatibility’’ is the result of in vitro experimentation. While much of this evidence is very persuasive of in vivo conse- quences, in many cases proof based on in vivo obser- vation is lacking. Thus, although ex vivo studies sug- gest the bioincompatible nature of conventional lactate-buffered PDF containing glucose (108– 110,164), data from long-term observations in PD pa- tients are required to definitively identify which PDF components have an impact (or not) on peritoneal host defense and the structure or function of the peritoneal membrane. Despite this lack of real in vivo evidence that PDF components directly affect peritoneal host defense or contribute to loss of membrane function, the weight of in vitro and ex vivo evidence, together with our in- creased understanding of the potential chronic effects of exposure to supra-physiological concentrations of PDF components, have resulted in the search for alter- native solution formulations. These alternative solution formulations can be divided into (a) those that replace or reduce glucose concentration with an alternative os- motic agent, e.g., polyglucose, glycerol, amino acids, or a combination of these, and (b) those that create a neutral or near neutral pH solution either by replacing lactate as a buffer and/or preparing the solutions in dual chamber bags such that the glucose can be sterilized separately, e.g., bicarbonate, bicarbonate in combina- tion with glycyl-glycine or lactate, or conventional lac- tate solution at pH 6.8 (165) (these solutions have the added advantage of reduced GDP content as a result of the sterilization of glucose at low pH). Many of these solutions have undergone phase II or phase III trials, and some have been introduced into clinical practice over the past few years. At present it is too early to assess whether any of these will impact on peritoneal membrane function. In vitro and ex vivo and animal studies, however, suggest that many of these formula- tions show significantly improved parameters of host defense compared to conventional acidic lactate- buffered solutions (107,110,122,166–173). It will be years, however, before the long-term effects of poten- tially more biocompatible PDF on peritoneal structure and function are definitively identified. Their introduc- tion, however, allows us a unique opportunity to assess their impact compared to conventional solutions on peritoneal membrane longevity. While there is strong theoretical, circumstantial, and in vitro evidence linking peritoneal damage to toxic or unphysiological constituents within dialysis fluid, prov- ing direct cause and effect has been difficult. This is due in part to the relatively long period over which peritoneal damage occurs and in part to the need, in the case of glucose, to use ever-increasing concentra- tions to maintain adequate fluid balance, thus setting up a viscious circle. It has often been noted that a rest from PD results in some recovery of ultrafiltration ca- pacity (38), and recent evidence from a group of pa- tients with severe ultrafiltration failure treated with glu- cose-free PD (glycerol and icodextrin) for several months found an improvement in both solute transport and sodium sieving (145). In another randomized trial using icodextrin versus glucose for the long day dwell in patients treated with automated peritoneal dialysis, those patients in the icodextrin group had a significant improvement in their ultrafiltration, although the mech- anism is less clear (22). It does seem likely, therefore, that strategies designed to avoid excessive glucose ex- posure may either reverse or prevent the development of peritoneal damage. 170 Davies et al. XI. WHAT WE DON’T UNDERSTAND ABOUT THE PROCESS OF PERITONEAL STRUCTURE/ FUNCTION CHANGES Although our understanding of ‘‘fibrotic’’ processes is increasing largely as a result of in vitro experiments, many questions remain about the mechanisms by which structural alterations in the peritoneum are ini- tiated and what factors are directly responsible or con- tributory to this process. In answering these questions we are severely hampered by the fact that there is no real description from PD patients of what these so- called ‘‘fibrotic’’ changes are or the time course over which they occur. Peritoneal biopsy data are to date very limited, and it is impossible to decide based on such a small uncontrolled sample size if the reported changes are representative for all patients. Clearly, there is the need to define the structure of the peritoneal membrane in normal, uremic, and dialyzed individuals and, where possible, to define the nature and time course of the changes that occur. Only then will we be able to define which factors contribute to membrane dysfunction and design therapeutic interventions to re- duce these negative consequences and increase perito- neal membrane longevity. XII. CONCLUSIONS This chapter has attempted to link what is currently known about peritoneal structure and function to the clinical problems experienced in the management of PD patients. As our understanding of this membrane improves, it provides us with an increasingly rational approach to therapeutic manipulation. Hopefully, this, combined with the increasing number of treatment op- tions available, should make it possible to enhance treatment quality and improve patient and technique survival on this modality. REFERENCES 1. Maiorca R, Cancarini GC, Camerini C, Brunori G, Manili L, Movilli E, Feller P, Mombelloni S. Is CAPD competitive with haemodialysis for long-term treat- ment of uraemic patients? [review]. Nephrol Dial Transplant 1989; 4:244–253. 2. Maiorca R, Vonesh E, Cavalli PL, De Vecchi A, Gian- grande A, La Greca G, Scarpione LL, Bragantini L, Cancarini GC, Cantaluppi A, Castelnova C, Castig- lioni A, Poisetti P, Viglino G. A multi-centre, selection adjusted comparison of patient and technique surviv- als on CAPD and hemodialysis. Perit Dial Int 1990; 11:118–127. 3. Fenton SSA, Schaubel DE, Desmeules M, Morrison HI, Mayo Y, Copleston P, Jeffrey JR, Kjellstrand CM. Hemodialysis versus peritoneal dialysis: a comparison of adjusted mortality rates. Am J Kidney Dis 1997; 30:334–342. 4. Lupo A, Tarchini R, Cancarini GC, Catizone L, Coc- chi R, De Vecchi A, Viglino G, Salomone M, Segoloni G, Giangrande A. Long-term outcome in continuous ambulatory peritoneal dialysis: a 10-year survey by the Italian Cooperative Peritoneal Dialysis Study Group. Am J Kidney Dis 1994; 24:826–837. 5. Davies SJ, Phillips L, Griffiths A, Russell L, Naish PF, Russell GI. What really happens to people on long-term peritoneal dialysis? Kidney Int. 54:2207– 2217. 6. Churchill DN, Taylor DW, Keshaviah PR. Adequacy of dialysis and nutrition in continuous peritoneal di- alysis: association with clinical outcome. J Am Soc Nephrol 1996; 7:198–207. 7. Twardowski ZJ, Nolph KD, Khanna R, Prowant BF, Ryan LP, Moore HL, Nielsen MP. Peritoneal equili- bration test. Perit Dial Bull 1987; 7:138–147. 8. Davies SJ, Bryan J, Phillips L, Russell GI. Longitu- dinal changes in peritoneal kinetics: the effects of peri- toneal dialysis and peritonitis. Nephrol Dial Transplant 1996; 11:498–506. 9. Gotloib L, Shostack A. Ultrastructural morphology of the peritoneum: new findings and speculations on transfer of solutes and water during peritoneal dialysis. Perit Dial Bull 1987; 7:119–129. 10. Gotloib L, Shostak A. The functional anatomy of the peritoneum as a dialysing membrane. In: Twardowski ZJ, Nolph KD, Khanna R, eds. Peritoneal Dialysis. New York: Churchill Livingstone, 1990:1–27. 11. Di Paolo N, Sacchi G, De Mia M, Gaggiotti E, Ca- potondo L, Rossi P, Bernini M, Pucci A, Sabatelli P, Alessandrini C. Morphology of the peritoneal mem- brane during continuous ambulatory peritoneal peri- toneal dialysis. Nephron 1986; 44:204–211. 12. Di Paolo N, Sacchi G, Buoncristiani V. The morphol- ogy of the human peritoneum in CAPD patients. In: Maher J, ed. Frontiers in Peritoneal Dialysis. New York: Field Rich, 1985:11–19. 13. Satoh K, Prescott SM. Culture of mesothelial cells from bovine pericardium and characterisation of their arachidonate metabolism. Biochim Biophys Acta 1987; 930:283–296. 14. Rennard SI, Jaurand M-C, Bignon J, Kawanami O, Ferrans VJ, Davidson J, Crystal RG. Role of pleural mesothelial cells in the production of the submeso- thelial connective tissue matrix of lung. Am Rev Re- spir Dis 1984; 130:267–274. 15. Gotloib L, Shostack A, Jaichenko J. Ruthenium-red- stained anionic charges of rat and mice mesothelial Peritoneal Membrane Failure 171 cell and basal lamina: the peritoneum is a negatively charged dialyzing membrane. Nephron 1988; 48:65– 70. 16. Gotloib L, Shustak A, Jaichenko J. Loss of mesothelial electronegative fixed charges during murine septic peritonitis. Nephron 1989; 51:77–83. 17. Beavis J, Harwood JL, Coles GA, Williams JD. Intra- peritoneal phosphatidyl choline levels in patients on continuous ambulatory peritoneal dialysis do not cor- relate with adequacy of ultrafiltration. J Am Soc Ne- phrol 1993; 3:1954–1960. 18. Beavis J, Harwood JL, Coles GA, Williams JD. Syn- thesis of phospholipids by human peritoneal mesothe- lial cells. Perit Dial Int 1994; 14:348–355. 19. Dobbie JW, Pavlina T, Lloyd J, Johnson RC. Phos- phatidylcholine synthesis by peritoneal mesothelium: its implication for peritoneal dialysis. Am J Kid Dis 1988; 12:31–36. 20. Jo¨rres A, Ludat K, Lang J, Sander K, Gahl GM, Frei U, DeJonge K, Williams JD, Topley N. Establishment and functional characterization of human peritoneal fi- broblasts in culture: regulation of interleukin-6 pro- duction by pro-inflammatory cytokines. J Am Soc Ne- phrol 1996; 72:2192–2201. 21. Beavis MJ, Williams JD, Hoppe J, Topley N. Human peritoneal fibroblast proliferation in 3-dimensional culture: modulation by cytokines, growth factors and peritoneal dialysis effluent. Kidney Int 1997; 51:205– 215. 22. Krediet RT, Ho-Dac-Pannekeet M, Struijk DG. Pres- ervation of peritoneal membrane function. Kidney Int 1996; 50:S62–S68. 23. Krediet RT, Zuyderhoudt FM, Boeschoten EW, Arisz L. Alterations in the peritoneal transport of water and solutes during peritonitis in continuous ambulatory peritoneal dialysis patients. Eur J Clin Invest 1987; 17: 43–52. 24. Krediet RT, Struijk DG, Koomen GC, Zemel D, Boes- choten EW, Hoek FJ, Arisz L. Peritoneal transport of macromolecules in patients on CAPD. Contrib Ne- phrol 1991; 89:161–174. 25. Blake PG, Flowerdew G, Blake RM, Oreopoulos DG. Serum albumin in patients on continuous ambulatory peritoneal dialysis—predictors and correlations with outcomes. J Am Soc Nephrol 1993; 3:1501–1507. 26. Rippe B, Stelin G, Haraldson B. Computer simulations of peritoneal fluid transport in CAPD. Kidney Int 1991; 40:315–325. 27. Monquil M, Imholz AL, Struijk DG, Krediet RT. Does impaired transcellular water transport contribute to net ultrafiltration failure during CAPD. Perit Dial Int 1995; 15:42–48. 28. Davies SJ, Brown B, Bryan J, Russell GI. Clinical evaluation of the peritoneal equilibration test. A pop- ulation based study. Nephrol Dial Transplant 1993; 8: 64–70. 29. Struijk DG, Krediet RT, Koomen GCM, Boeschoten EW, Hoek FJ, Arisz L. A prospective study of peri- toneal transport in CAPD patients. Kidney Int 1994; 45:1739–1744. 30. Durand P-Y, Chanliau J, Gamberoni J, Hestin D, Kessler M. Intraperitoneal hydrostatic pressure and ul- trafiltration volume in CAPD. Adv Perit Dial 1993; 9: 46–48. 31. Struijk DG, Imholz AL, Krediet RT, Koomen GC, Ar- isz L. Use of the disappearance rate for the estimation of lymphatic absorption during CAPD [review]. Blood Purif 1992; 10:182–188. 32. Imholz AL, Koomen GC, Struijk DG, Arisz L, Krediet RT. Effect of an increased intraperitoneal pressure on fluid and solute transport during CAPD. Kidney Int 1993; 44:1078–1085. 33. Steinhauer HB, Schollmeyer P. Prostaglandin medi- ated loss of proteins during peritonitis in continuous ambulatory peritoneal dialysis. Kidney Int 1986; 29: 584–590. 34. Pannekeet MM, Mulder JB, Weening JJ, Struijk DG, Zweers MM, Krediet RT. Demonstration of aquaporin- CHIP in peritoneal tissue of uremic and CAPD pa- tients. Perit Dial Int 1996; 16(suppl 1):S54–7. 35. Heimburger O, Waniewski J, Werynski A, Tranaeus A, Lindholm B. Peritoneal transport in CAPD patients with permanent loss of ultrafiltration capacity. Kidney Int 1990; 38:495–506. 36. Struijk DG, Krediet RT, Koomen GC, Hoek FJ, Boes- choten EW, Reijden HJ, Arisz L. Functional charac- teristics of the peritoneal membrane in long-term con- tinuous ambulatory peritoneal dialysis. Nephron 1991; 59:213–220. 37. Blake PG, Abraham G, Sombolos K, Izatt S, Weiss- garten J, Ayiomamitis A, Oreopoulos DG. Changes in peritoneal membrane transport rates in patients on long term CAPD. Adv Perit Dial 1989; 5:3–7. 38. Selgas R, Fernandez-Reyes MJ, Bosque E, Bajo MA, Borrego F, Jimenez C, Del Peso G, de Alvaro F. Func- tional longevity of the human peritoneum: how long is continuous peritoneal dialysis possible? Results of a prospective medium long-term study. Am J Kidney Dis 1994; 23:64–73. 39. Davies SJ, Phillips L, Russell GI. Peritoneal solute transport predicts survival on CAPD independently of residual renal function. Nephrol Dial Transplant 1998; 13:962–968. 40. Gotloib L, Shostack A, Bar-Sella P, Cohen R. Contin- uous mesothelial injury and regeneration during long term peritoneal dialysis. Perit Dial Bull 1987; 7:148– 155. 41. Di Paolo N, Sacchi G. Peritoneal vascular changes in continuous ambulatory peritoneal dialysis (CAPD): an in vivo model for the study of diabetic microangio- pathy. Perit Dial Int 1989; 9:41–45. 42. Dobbie J, Zaki M, Wilson L. Ultrastructural studies on the peritoneum with special reference to chronic 172 Davies et al. ambulatory peritoneal dialysis. Scott Med J 1981; 26: 213–223. 43. Dobbie J, Lloyd J, Gall C. Categorization of ultra- structural changes in peritoneal mesothelium, stroma and blood vessels in uremia and CAPD patients. In: Khanna R, Nolph K, Prowant B, Twardowski Z, Or- eopoulos D, eds. Toronto: Perit Dial Int Inc., 1990:3– 12. 44. Dobbie JW. Pathogenesis of peritoneal fibrosing syn- dromes (sclerosing peritonitis) in peritoneal dialysis. Perit Dial Int 1992; 12:14–27. 45. Dobbie JW. Ultrastructure and pathology of the peri- toneum in peritoneal dialysis. In: Gokal R, Nolph KD, eds. The Textbook of Peritoneal Dialysis. Dordrecht: Kluwer Academic Publishers, 1994:17–44. 46. Coles GA. Immunoglobulin and complement. Contrib Nephrol 1990; 85:24–29. 47. Coles GA, Minors SJ, Horton JK, Fifield R, Davies M. Can the risk of peritonitis be predicted for new continuous ambulatory peritoneal dialysis (CAPD) pa- tients? Perit Dial Int 1989; 9:69–72. 48. Coles GA, Alobaidi HMM, Topley N, Davies M. Op- sonic activity of dialysis effluent predicts those at risk of Staphylococcus epidermidis peritonitis. Nephrol Dial Transplant 1987; 2:359–365. 49. Holmes C, Lewis S. Host defense mechanisms in the peritoneal cavity of continuous ambulatory peritoneal dialysis patients. 2. Humoral defenses. Perit Dial Int 1991; 11:112–117. 50. Holmes CJ. Peritoneal host defense mechanism in peritoneal dialysis. Kidney Int 1994; 46:S58–S70. 51. Zemel D, ten Berge RJM, G. SD, Bloemena E, Koo- men GCM, Krediet RT. Interleukin-6 in CAPD pa- tients without peritonitis: relationship to the intrinsic permeability of the peritoneal membrane. Clin Ne- phrol 1992; 37:97–103. 52. Zemel D, ten Berge RJM, Koomen GCM, Struijk DG, Krediet RT. Serum interleukin-6 in continuous am- bulatory peritoneal dialysis patients. Nephron 1993; 64:320–321. 53. Zemel D, Krediet RT, Koomen GCM, Kortekaas WMR, Geertzen HGM, ten Berge RJM. Interleukin-8 during peritonitis in patients treated with CAPD; an in vivo model of acute inflammation. Nephrol Dial Transplant 1994; 9:169–174. 54. Zemel D, Koomen GCM, Hart AAM, ten Berge RJM, Struijk DG, Krediet RT. Relationship of TNF ␣ , inter- leukin-6, and prostaglandins to peritoneal permeability for macromolecules during longitudinal follow-up of peritonitis in continuous ambulatory peritoneal dialy- sis. J Lab Clin Med 1994; 122:686–696. 55. Zemel D, Imholz ALT, de Wart DR, Dinkla C, Struijk DG, Krediet RT. The appearance of tumor necrosis factor- ␣ and soluble TNF-receptors I and II in peri- toneal effluent during stable and infectious CAPD. Kidney Int 1994; 46:1422–1430. 56. Zemel D, Betjes MGH, Dinkla C, Struijk DG, Krediet RT. Analysis of inflammatory mediators and peritoneal permeability to macromolecules shortly before the on- set of overt peritonitis in patients treated with CAPD. Perit Dial Int 1994; 15:134–141. 57. Moutabarrik A, Nakanishi I, Namiki M, Tsubakihara Y. Interleukin-1 and its naturally occurring inhibitor in peritoneal dialysis patients. Clin Nephrol 1995; 43: 243–248. 58. Brauner A, Hylander B, Wretlind B. Interleukin-6 and interleukin-8 in dialysate and serum from patients on continuous ambulatory peritoneal dialysis. Am J Kid Dis 1993; 22:430–435. 59. Brauner A, Hylander B, Wretlind B. Tumor necrosis factor- ␣ , interleukin-1 ␤ , and interleukin-1 receptor an- tagonist in dialysate and serum from patients on con- tinuous ambulatory peritoneal dialysis. Am J Kid Dis 1996; 27:402–408. 60. Topley N, Jo¨rres A, Mackenzie R, Coles GA, Williams JD. Interactions of macrophages and mesothelial cells in peritoneal host defence. Nieren Hochdruckkr 1994; 23:S88–S91. 61. Topley N, Davenport A, Li F-K, Fear H, Williams JD. Activation of inflammation and leukocyte recruitment into the peritoneal cavity. Kidney Int 1996; 50:S17– S21. 52. Duwe AK, Vas SI, Weatherhead JW. Effects of the composition of peritoneal dialysis fluid on chemilu- minescence, phagocytosis and bactericidal activity in vitro. Infect Immun 1981; 33:130–135. 63. Alobaidi HM, Coles GA, Davies M, Lloyd D. Host defence in continuous ambulatory peritoneal dialysis: the effect of the dialysate on phagocyte function. Ne- phrol Dial Transplant 1986; 1:16–21. 64. Alobaidi H. Host Defence in CAPD: A Laboratory and Clinical Investigation. University of Wales, 1986. 65. Topley N, Alobaidi HM, Davies M, Coles GA, Wil- liams JD, Lloyd D. The effect of dialysate on perito- neal phagocyte oxidative metabolism. Kidney Int 1988; 34:404–411. 66. Topley N, Mackenzie R, Jo¨rres A, Coles GA, Williams JD. Cytokine networks in CAPD: interactions of res- ident cells during inflammation in the peritoneal cav- ity. Perit Dial Int 1993; 13:S282–S285. 67. Topley N, Williams JD. Effect of peritoneal dialysis on cytokine production by peritoneal cells. Blood Purif 1996; 14:188–197. 68. Topley N, Petersen MM, Mackenzie R, Kaever V, Neubauer A, Stylianou E, Coles GA, Davies M, Jo¨rres A, Williams JD. Human peritoneal mesothelial cell prostaglandin synthesis: induction of cyclooxygenase mRNA by peritoneal macrophage derived cytokines. Kidney Int 1994; 46:900–909. 69. Topley N, Jo¨rres A, Luttmann W, Petersen M, Lang M, Thierausch K-H, Mu¨ller C, Coles G, Davies M, Williams J. Human peritoneal mesothelial cells syn- [...]... Failure 128 129 130 131 132 133 134 135 136 137 138 139 Witowski J, Williams JD, Topley N D-Glucose induces transforming growth factor-b1 (TGF-b1) mRNA expression and secretion in human peritoneal mesothelial cells (HPMC): effect of hyperosmolality Peritoneal Dialysis International In press Fujimori A, Naito H, Miyazaki T, Azuma M, Hashimoto S, Horikawa S, Tokukoda Y Elevation of interleukin-6 in the dialysate... Dial Int 1996; 16 :34 5 34 6 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 Vonesh EF, Moran J Discrepancy between urea KT/ V versus normalized creatinine clearance Perit Dial Int 1997; 17: 13 16 Vonesh EF Consequences of normalizing peritoneal dialysis dose Semin Dial 1997; 10:2 93 294 Tzamaloukas AH, Vonesh EF Urea clearance, creatinine clearance and size indicators in peritoneal dialysis Semin Dial... effect of a high peritoneal equilibration rate Renal Failure 1995; 17(5):575–587 Holley JL Patient-reported symptoms and adequacy of dialysis as measured by creatinine clearance Perit Dial Int 19 93; 13( suppl 2):S219–S220 Tzamaloukas AH, Murata GH, Sena P Assessing the adequacy of peritoneal dialysis Perit Dial Int 19 93; 13: 236 – 238 DeAlvaro F, Bajo MA, Alvarez-Ude F, et al Adequacy of peritoneal dialysis: ... Delivered Dialysis Dose 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 Bergstrom J Appetite in CAPD patients Perit Dial Int 1995; 15(suppl 3) :S181-S184 Ikizler TA, Greene JH, Wingard RL, Parker DA, Hakim RM Spontaneous dietary protein intake during progression of chronic renal failure J Am Soc Nephrol 1995; 6: 138 6– 139 1 Jones MR Etiology of severe malnutrition: results of an international cross-sectional... Transplant 19 93; 8: 535 – 538 Brandes JC, Piering WF, Peres JA, Blumenthal JS, Fritsche C Clinical outcome of continuous ambulatory peritoneal dialysis predicts urea and creatinine kinetics J Am Soc Nephrol 1992; 2:1 430 –1 435 Arkouche W, Delawari E, My H, Laville M, Abdullah E, Traeger J Quantification of adequacy of peritoneal dialysis Perit Dial Int 19 93; 13( suppl 2):S215–S218 Heaf J CAPD adequacy and dialysis. .. Practice of Dialysis Baltimore: Williams and Wilkins 1994:111–129 Ronco C Adequacy of peritoneal dialysis is more than Kt/V Nephrol Dial Transplant 1997; 12(suppl 1):68– 73 190 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Tzamaloukas and Golper Chatoth DK, Golper TA, Gokal R In-depth review: morbidity and mortality in defining adequacy of peritoneal dialysis: a step beyond NKF-DOQI Am J Kidney Dis 1999; 33 :617– 632 ... ( 23) Inverse correlation of clearances with hospitalization rate (7,8,24) Inverse correlation of clearances with symptom score ( 23 29) Problems Lack of correlation between clearances and symptoms (30 34 ) Lack of specificity and sensitivity of uremic symptoms (35 ,36 ) Malnutrition Supportive evidence of link with small solute clearances Frequency of anorexia in renal failure (37 ) Association between inadequate... Immunohistochemical studies of the peritoneal membrane and infiltrating cells in normal subjects and in patients on CAPD Kidney Int 1994; 46:4 43 454 Robson RL, Witowski J, Loetscher P, Topley N Differential regulation of C-C and C-x-C chemokine syn- 1 73 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 thesis in cytokine-activated human peritoneal mesothelial cells by IFN-␥ Kidney Int 1997; 52:11 23 Topley N Membrane... 70 71 72 73 74 75 76 77 78 79 80 81 82 83 thesize IL-6: induction by IL-1␤ and TNF␣ Kidney Int 19 93; 43: 226– 233 Topley N, Brown Z, Jorres A, Westwick J, Coles GA, ¨ Davies M, Williams JD Human peritoneal mesothelial cells synthesize IL-8: synergistic induction by interleukin-1␤ and tumor necrosis factor ␣ Am J Pathol 19 93; 142:1876–1886 Liberek T, Topley N, Luttmann W, Williams JD Adherence of neutrophils... chapter will focus on complications of PD that relate to inadequate delivered dose of dialysis, focusing on the consequences of poor azotemic control, its recognition, and I SMALL SOLUTE CLEARANCE AS AN INDEX OF AZOTEMIC CONTROL It is now clear that the blood levels of azotemic indices are poor indicators of control of uremia by PD or HD Patients with very low rates of removal of urea and creatinine . regulation of C-C and C-x-C chemokine syn- thesis in cytokine-activated human peritoneal meso- thelial cells by IFN- ␥ . Kidney Int 1997; 52:11 23. 84. Topley N. Membrane longevity in peritoneal dialysis: impact. Weatherhead JW. Effects of the composition of peritoneal dialysis fluid on chemilu- minescence, phagocytosis and bactericidal activity in vitro. Infect Immun 1981; 33 : 130 – 135 . 63. Alobaidi HM, Coles. sterilised PD-fluids impair growth and inflammatory responses of cultured cell lines and human leukocytes. Clin Nephrol 19 93; 39 : 34 3 34 8. 117. Lamb EJ, Cattell WR, Dawnay ABSJ. In vitro for- mation of advanced