Peritoneal dialysis (PD) uses the peritoneal membrane as a semi-permeable membrane for solute transfer and ultrafiltration. The properties of this membrane are important determinants for selecting the optimal treatment regimen but vary among individuals as well as within the same individual over time (for review, see Coester et al. [1]). As such, evaluation of the peritoneal membrane characteristics is of importance to guide PD prescription management (Figure 1). So far, the European Best Practice Guidelines (EBPG) have not covered the evaluation of the peritoneal membrane, but other guideline bodies have done so [2–4]. Flowchart of clinical peritoneal membrane characteristics evaluation. The present document summarizes the point of view of the European Renal Best Practice (ERBP) advisory board on this topic. In accordance with the mission statement of ERBP [5], this position statement is not a guideline, which would necessitate a complete in-depth analysis of the literature, but reflects recommendations and/or clinical advice on how to evaluate peritoneal membrane characteristics in clinical practice and how the results should be incorporated in PD prescription. The recommendations/clinical advice are based on expert opinions, supported by evidence when available. 1.1 An evaluation of peritoneal membrane characteristics should be used to guide prescription of PD therapy and follow the evolution of peritoneal membrane function over time. 1.2 An evaluation of peritoneal membrane characteristics should routinely be repeated at least once per year or when new clinical problems (overhydration, malnutrition, metabolic disturbances) are noticed. 1.3 PD prescriptions should be optimized according to Table 1 in function of the results of the peritoneal membrane characteristics. To optimize treatment prescription with regard to small-solute clearance, volume regulation and reduction of uraemic toxicity. To assess membrane characteristics not related to small solutes: osmotic conductance of glucose, aquaporins, hydraulic conductance, large-solute flow, lymphatic reabsorption. To evaluate the evolution of peritoneal function over time. Assessment of peritoneal membrane characteristics, specifically solute transport rate and ultrafiltration capacity, is fundamental to PD prescription, as this will guide prescription. There is considerable between-patients variability in both solute transport and ultrafiltration capacity. These differences necessitate that a therapy should be tailored to the specific needs of the patient in terms of the ideal length of dwell, the number of dwells and the type of dialysis solution used (Table 1). An inappropriate prescription can lead to substantial underachievement in terms of solute clearance and ultrafiltration or unnecessary exposure to hypertonic solutions. There is, for example, evidence that part of the higher mortality associated with a fast transport status can be abolished by using appropriate prescriptions [6,7] and that using automated peritoneal dialysis (APD) in slow transporters results in hypertension [8]. It is suggested that 4–6 weeks after start of PD is the appropriate timing for a first evaluation. Peritoneal membrane transport types and their consequences for clinical management Peritoneal membrane transport types and their consequences for clinical management Membrane characteristics change with time on therapy. Some PD patients will develop changes to the peritoneal membrane consisting of neo-angiogenesis, vasculopathy and submesothelial and interstitial fibrosis [9]. In the majority of these patients, these alterations will lead to decreased ultrafiltration capacity and an increase in the transport rate for small solutes [10,11]. Therefore, membrane transport characteristics should be evaluated at least once a year to make sure the prescription still matches the needs of the patient. Deterioration of clinical (volume overload, ultrafiltration failure and malnutrition) and biochemical parameters (haemoglobin, serum albumin, urea and creatinine) can be caused by an inappropriate PD regimen, as a consequence of a change in peritoneal membrane characteristics. When these problems arise, re-evaluation of the peritoneal membrane characteristics should be performed to adapt the treatment regimen accordingly. 2.1 There is insufficient evidence to prefer one test of peritoneal membrane characteristics over another for clinical prescription. However, some tests may render specific information not provided by the classical peritoneal equilibration test (PET) test (Table 2a). The type of test to be used is thus dependent on the type of information one wants to obtain and the question one wishes to be answered (Table 2b). 2.2 As evidence is scarce, ERBP strongly recommends and supports epidemiological follow-up of the relation between peritoneal membrane characteristics, patient characteristics, treatment parameters and outcome. Some basic parameters of peritoneal membrane characteristics can be directly derived from observing ultrafiltration volumes obtained with the regular PD schedule of the patient, as indicated in Table 1. The original PET (see Appendix 1 for instructions on how to perform a classic PET) is the most widely used test for evaluation of peritoneal membrane characteristics [12,13]. The original PET used a fixed fill volume of 2 l of a 2.27% glucose solution over a 4-h dwell. There is no evidence that using 1.36% or 3.86% glucose instead of 2.27% glucose influences the results of dialysate over plasma ratio of creatinine (D/Pcreat) or ratio of glucose concentration at a given moment over that at the start of the dwell (D/D0) [14–16]. The impact of a preceding overnight dwell with icodextrin has only been evaluated in one study, showing a small increment in D/P value. This was, however, a small study, so no definite recommendation can be made in this regard [17]. Although the original PET allows accurate estimation of small-solute transport, as expressed by D/Pcreat and D/D0, and ultrafiltration capacity, it does not provide sufficient information to discriminate between causes of ultrafiltration failure. To answer the latter question, using a 3.86% glucose solution during the PET is recommended [18] to determine the evolution of D/Psodium during the dwell. This allows evaluation of the function of the aquaporins by the assessment of ‘sodium sieving’ [15,19]. This test has been named ‘modified PET’ ( Appendix 2). Of note, the timing and amplitude of sodium sieving depend on the peritoneal transport characteristics of small solutes through the small pores [19]. The sodium dip results from a competition between free water transport over the aquaporins and the diffusion of sodium over the small pores [20]. In the first part of the dwell, the osmotic gradient over the aquaporins is strongest and gradually decreases as glucose is absorbed. The free water transport is thus most pronounced in the beginning of the dwell. In the second part of the dwell, diffusive transport of sodium from the plasma to the dialysate will increase as a consequence of the increase in concentration difference (see Appendix 3). Therefore, using the 1-h value of D/Psodium to estimate the free water transport is advocated [21,22], a procedure named the mini PET. When the mini PET is performed once with a 1.36% and once with a 3.86% glucose solution, it is possible to calculate the osmotic conductance to glucose. This test has been called the ‘double mini PET’ [23] ( Appendix 2). Whereas the (double) mini PET is short and gives important information on aquaporin function, it fails to provide estimates of net fluid reabsorption from the peritoneal cavity. As this can be a cause of ultrafiltration failure, a mini PET should preferentially be coupled to an original or modified PET. Although the double mini PET is somewhat more complex and labourious, it provides interesting and essential information, especially related to osmotic conductance for glucose, which is the capacity of glucose to induce transperitoneal ultrafiltration through generation of osmotic pressure. This is especially important as it allows detection of intrinsic changes in the peritoneal membrane, such as sclerosis or fibrosis [24], which might be more prevalent as a cause of ultrafiltration than aquaporin deficiency. In addition, the calculation of the osmotic conductance does not require measurement of sodium concentrations in dialysate, a lab test that might be difficult to obtain in clinical routine labs. For all these reasons, measuring osmotic conductance for glucose performing a double mini PET without sodium modelling has great appeal as a second line test after PET evaluation in complicated cases of ultrafiltration (UF) failure. 2.3 In scientific publications, one should avoid reporting the results of PET only as transport categories. Expression of data as exact figures of D/P (dialysate over plasma) ratios is recommended. For clinical use and prescription management, the current terminology should be replaced by the more relevant descriptions ‘fast’, ‘average’ and ‘slow’, as these terms more intuitively relate to the optimal dwell length. Although the reporting of transport categories is widespread, their relevance as comparators between populations and studies is to be debated, as large differences exist in distributions of transport characteristics between populations [25,26]. The terms ‘high’ and ‘low’ transporter should be avoided. They create confusion, as they suggest that ‘high’ or ‘low’ transporters have a high or low solute removal, respectively, which is often not the case because of loss of the osmotic solute gradient resulting in negative ultrafiltration and thus decreased drained volumes in ‘high’ transporters [25] (see Appendix 4). As a consequence, solute removal is lower in ‘high’ transporters than in ‘low’ transporters. It would therefore be more realistic and representative to use the terms ‘fast’ and ‘slow’ since, in fact, a rate of transport is being measured. In clinical practice, the division into four categories to guide prescription is unnecessarily complex, as ‘average slow’ and ‘average fast’ patients can be treated with comparable treatment regimens. In view of the above, prescription recommendations for clinical practice should be based on the classification ‘fast’, ‘average’ and ‘slow’ transporter status. This categorization can be obtained even based on simple clinical observation. As such, the classification is more based on ‘general’ appreciation than on absolute D/P values. Fast transporters typically have a fast equilibration of creatinine and a fast dissipation of the glucose gradient, with thus a negative ultrafiltration in dwells longer than 180 min with 1.36% glucose. Slow transporters have a slow equilibration of creatinine and a slow dissipation of glucose but a sustained ultrafiltration even after a dwell longer than 300 min with a 1.36% glucose solution. 2.4 D/Purea shows far less variability between patients than D/P of larger molecules. As such, when formal evaluation of the peritoneal membrane characteristics is required, the use of D/Pcreat should be preferred to obtain better characterization of the small-solute transport characteristics of the membrane. 2.5 When applying tests of peritoneal membrane characteristics, some methodological caveats should be considered. High glucose concentrations might interfere with the determination of creatinine. Methods to avoid this interference or correction factors should be used accordingly. Enzymatic determination of creatinine is recommended (both in plasma as in dialysate) when available. Determination of sodium concentration in dialysate can be biased by the methodology used because of the presence of glucose and the absence of proteins and lipids in the dialysate. The preferred method is flame photometry. Indirect ion-selective electrodes can be used when they have been calibrated against flame photometry using peritoneal dialysate fluid as reference [27]. The fill volume used can potentially influence the obtained results. Using too-low fill volumes can falsely induce the impression of a fast transport status. Fill volumes should be adapted to body surface area, not to weight [28–31]. For the testing of the peritoneal membrane transport characteristics, using the usual fill volume of the individual patient is recommended, as this reflects what is going on in this patient in clinical practice. It should be considered, however, that changing fill volume can change the observed transport status. When calculating ‘ultrafiltration’ capacity, the potential overfill of bags should be taken into account [32]. Indeed, most companies overfill their bags during the production process. Classically, this amounts up to 200 ml/exchange, but actual weighing of the bags before and after the dwell is recommended. This procedure also corrects for differences induced by the flush before fill procedure, as the flushed volume is accounted both at the in- and outside. When the bags are only weighed after drainage and not before filling, ultrafiltration will be overestimated, as the flush before fill rinsing volume will be added to the drained weight, whereas this is not ultrafiltered volume. 2.6 Peritoneal membrane ultrafiltration failure is defined as a drained volume after a 4-h dwell of <2100 ml with a 2.27% glucose solution or one of <2400 ml with a 3.86% glucose solution, respectively (International Society of Peritoneal Dialysis ISPD guideline [18]). The (theoretical) condition ‘ultrafiltration failure’ should be distinguished from the (clinical) condition ‘overhydration’. Clinical overhydration is the net result of the volume balance of the patient and, as such, is influenced not only by peritoneal ultrafiltration capacity but also by other factors, such as residual urine production and dietary salt and fluid intake. When analysing causes of overhydration, non-membrane-associated factors should also be evaluated: dietary compliance, evolution of residual renal function and diuresis and mechanical causes. Mechanical causes (bad drainage or leakage) should be the first mechanisms to be suspected when a long dwell with icodextrin results in negative ultrafiltration. Net fluid loss from the peritoneum can occur through several mechanisms, including capillary fluid reabsorption via the Starling mechanism, true lymphatic reabsorption and local entry of fluid into the tissues. The sum of these can be measured using volume markers such as dextran as in the peritoneal assessment test or with the Dialysis test The however, be by However, peritoneal fluid reabsorption can be suspected when mechanical problems leakage) have been and icodextrin results in ultrafiltration. on the importance of high rate of peritoneal fluid loss as a cause of ultrafiltration failure in large are In a study, more than of cases of ultrafiltration failure a high peritoneal fluid loss of peritoneal function tests relevant for routine clinical practice free water osmotic of peritoneal function tests relevant for routine clinical practice free water osmotic peritoneal function test to assess peritoneal equilibration dialysis capacity peritoneal function test to assess peritoneal equilibration dialysis capacity For optimal PD prescription management, parameters related to peritoneal membrane characteristics should also be considered. important is the that should be on a regular The drainage is an important to guide prescription management, especially in It should be taken into account that drainage time is in time. As most patients have a drainage with a part of the rate and a more part at the and as especially at the of drainage no diffusion is the dialysate should be For a drained dialysate can be ( Appendix of should be avoided. This can be by the number of dwells low and by after the than complete drainage can in most be done using the renal function, both in terms of clearance as in terms of should be on a regular by urine and calculation of the of urea and creatinine renal function is not only an important of it is also an important to into account when a peritoneal dialysis regimen prescription. with a residual renal function often also have a of the peritoneal membrane. It is strongly to patients to residual renal also results in a of residual renal function and is by an important to should be it can also cause of residual renal Peritoneal loss should be measured as an important Peritoneal loss is a of and, as such, a of or of It is an important of in PD patients It should be taken into account that this type of patients to does not their Peritoneal loss can be to discriminate fast transport status as caused by large surface from fast transport status to However, it has to be that this does not recommendations for prescription. Of note, prescription recommendations not PD peritoneal or should be as this is a the recommendations on the of the dwells are all patients can or in function of their and When negative ultrafiltration is and mechanical causes and lymphatic reabsorption have been the dwell time than glucose concentration is As fast dissipation of osmotic of the peritoneal and equilibration between plasma and peritoneum this will result in a more optimal ultrafiltration and solute removal, unnecessary glucose In patients on with as with an drained PD time a residual volume to that at the should be considered. the and are of the ERBP of the ERBP advisory board are and This document has been by the of ERBP and by the of The classic PET uses ml of a 2.27% glucose solution as The test is performed in the to the with their overnight dwell fluid still in the The fluid is and after complete the ml is after of the the patient is to over several to the fluid and a small dialysate is drained for time point 2 a new dialysate is taken and also a a new dialysate is all creatinine and glucose are The results are in a PET the ratio of the dialysate glucose concentration at a time over the dialysate glucose concentration in the the dialysate over plasma ratio of creatinine in the and time in the 1. The modified PET drainage min at of the dialysate of the overnight dwell. 3.86% glucose solution should be used for the the bags and the before the beginning of the The weighing should be repeated at the of the test in to assess the volume. of the to the patient and of solution. the of patient over several and ml in the dialysate in the drained This dialysate is new dialysate is taken in a comparable after min for dialysate creatinine and glucose and after and min for dialysate glucose and a complete drainage is and the bags are is taken after min for plasma glucose, plasma plasma plasma sodium and plasma sieving is expressed as being the difference in concentration between the dialysate at and the dialysate drained after The double mini PET (for see drainage min at of the dialysate of the overnight dwell in a and measurement of the volume of the overnight dwell. 1.36% glucose solution should be used for the first and a 3.86% glucose solution for the second part of the of the bags and of the before the beginning of the The weighing should be repeated at the of the test in to assess the volume. of the to the patient and of solution ml of it in the min after the of the complete drainage of the cavity. of the dialysate volume. dialysate should be taken for analysis of glucose and for plasma glucose, plasma plasma plasma sodium and plasma is as after min of the test with the 3.86% solution, being the difference in concentration between the solution and the dialysate drained after is the during the second part of the test with the 3.86% solution. is as The value is a correction for the that not at the beginning of the dwell, but only after and for the of the glucose in the dialysate by conductance for glucose the of glucose to an osmotic sufficient to cause transperitoneal ultrafiltration. It is a being by the surface and by the of glucose. It will thus be influenced by changes in to higher by aquaporin function determine the and by properties of the presence of fibrosis the interstitial in patients with and interstitial osmotic conductance will In the by et an osmotic conductance 2 associated with ultrafiltration failure. In the patients without ultrafiltration failure, the osmotic conductance sieving is the of sodium concentrations in the dialysate in the first of a PD dwell. This is induced by the that aquaporins only transport of water and not of In the first part of a dwell, is a osmotic gradient over the aquaporins, free water transport from the to the dialysate and resulting in a of dialysate sodium In the part of the dwell, the increase in concentration difference for sodium between the dialysate and the plasma will result in diffusive transport of sodium over the small and sodium concentration in the dialysate will from et al. As a consequence, this ‘sodium can be used to evaluate the of the The the osmotic gradient over the aquaporins, the more pronounced the sodium dip will Therefore, a 3.86% hypertonic glucose is the preferred solution to test sodium An or decreased sodium dip can be to decreased aquaporin function but can also be to a fast diffusive Although these can be by calculating the free water clearance, with the double mini in clinical practice it is more to on a simple of when is a decreased or sodium dip with a 3.86% glucose solution and a high ultrafiltration with a icodextrin dwell, the cause is fast diffusive When ultrafiltration with a icodextrin dwell is the cause is most aquaporin deficiency. For more of ultrafiltration failure, measuring osmotic conductance by of a double mini PET should be recommended. It is in to determine osmotic conductance, it is not to sodium in the dialysate. When one also wants to free water clearance sodium it is to determine sodium concentrations in the plasma and in the dialysate. Of note, the between free water clearance and sodium removal thus the sodium with of the dialysate solution and decreases with diffusive transport rate and the of the dwell. As such, sodium sieving is not in fast transporters with short dwells but can be substantial in slow transporters with short dialysate volume dwell time. high transport transport transport low transport 1 the evolution of volume after of 2 l of 3.86% glucose solution in patients with transport status. It can be observed that patients with ‘high’ transport status have a to have lower volumes as to with high low of low transport status. 2 removal of urea during one dwell in the same It can be observed to the lower drained have lower removal of urea as to the high low and low transporters. Therefore, it would be more to peritoneal membrane transport characteristics for small solutes as ‘fast’ and ‘slow’ than as ‘high’ and ‘low’ from et al. Peritoneal can be measured and as a or as rate over time from et al. For a the volume is in the and time on the the volume is time it is indicated how volume has been drained by weighing the drainage and this is from the volume and For the rate have the rate in the and the time in the rate is measured by weighing the drainage and calculating the of volume drained per It can be observed that it more time to the ml than to the the moment that the changes is no more of a sufficient volume of dialysate with the peritoneal as a consequence, is also no clearance, and thus is no patient characteristics, this can substantial loss of treatment time especially in This loss of treatment time can be by the to drainage after the has been after which a new fill can This treatment can in some be on in it can be obtained by using the In the latter the should to the volume obtained at the
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Biesen et al. (2010) studied this question.