Peritoneal equilibration test

INTRODUCTION — 

The peritoneal equilibration test (PET) is a semiquantitative assessment of peritoneal membrane transport function in patients on peritoneal dialysis [1,2]. The solute transport rates are assessed by the rates of their equilibration between the peritoneal capillary blood and dialysate. The ratio of solute concentrations in dialysate and plasma (D/P ratio) at specific times (t) during the dwell signifies the extent of solute equilibration. This ratio can be determined for any solute that is transported from the capillary blood to the dialysate. Creatinine, urea, electrolytes, phosphate, and proteins are the commonly tested solutes for clinical use.

Since glucose is absorbed from the dialysate to blood and very quickly metabolized, a conventional D/P ratio for glucose is meaningless. Instead, the fraction of glucose absorbed from the dialysate at specific times can be determined by the ratio of dialysate glucose concentrations at specific times (t) to the initial level in the dialysis solution (Dt/D0). The PET also helps measure ultrafiltration (UF) and residual volumes [3,4].

An overview of the PET is presented here. A detailed analysis of the utility of this examination in evaluating patients with inadequate clearances or UF is presented separately. (See "Inadequate solute clearance in peritoneal dialysis", section on 'Peritoneal equilibration test' and "Management of hypervolemia in patients on peritoneal dialysis", section on 'Peritoneal equilibration test'.)

ELEMENTS OF THE PERITONEAL EQUILIBRATION TEST — 

The PET is a highly reproducible procedure consisting of a standardized four-hour dialysis exchange with a dialysis solution [5]. The test permits the comparison of multiple results in a patient over a long period of therapy; in addition, the results between patients within a center and between populations from different geographic locations may be compared.

The PET is standardized for the following elements [3]:

●Duration of preceding exchange prior to the test

●Inflow volume

●Positions during inflow, drain, and dwell

●Durations of inflow and drain

●Sampling method and processing

●Laboratory assays

It is extremely important to adhere to the standard test regimen [6,7]. In one study, variations in the performance of the preceding exchange prior to the test, such as utilizing a dry, tidal, or standard exchange, resulted in significantly different results [6]. There are data, however, to suggest that it is not mandatory to have a preceding dwell time of 12 hours [8]. Despite these data, we perform a PET after an overnight pre-exchange of 8 to 12 hours dwell time.

Among individual patients, the PET should always be done using the same dialysate so that longitudinal comparisons are possible. However, the use of conventional versus biocompatible dialysate does not appear to alter the interpretation of results [9].

Procedure — The standardized four-hour PET procedure consists of the following sequential steps:

●An overnight 8 to 12 hour pre-exchange is performed.

●While the patient is in an upright position, the overnight exchange is drained (drain time not to exceed 25 minutes).

●Two liters of dialysis solution (2.5 or 4.25 percent dextrose) [10] are infused over 10 minutes with the patient in the supine position. The patient is rolled from side to side after every 400 mL infusion.

●After the completion of infusion (0 time) and at 120 minutes dwell time, 200 mL of dialysate is drained. A 10 mL sample is taken, and the remaining 190 mL is infused back into the peritoneal cavity.

●During the four-hour dwell time, the patient is upright and allowed to freely ambulate.

●A serum sample is obtained at 120 minutes.

●At the end of the dwell (240 minutes), the dialysate is drained in the upright position (drain time not to exceed 20 minutes).

●The drain volume is measured, and a 10 mL sample is taken from the drain.

●All the samples are sent for solute measurement (creatinine, urea, and glucose).

●The serum and dialysate creatinine concentrations are corrected for a high glucose level, which contributes to noncreatinine chromogens during the creatinine assay; however, a single glucose correction factor cannot be applied to both conventional and low glucose degradation product (GDP) solutions [11].

●The Dt/D0 glucose and the dialysate to plasma (D/P) ratios for creatinine, urea, and others are calculated.

The standardized test for clinical utility measures dialysate creatinine and glucose levels at zero, two, and four hours of dwell and serum levels of creatinine and glucose at any time during the test. The extensive unabridged test, which was originally proposed by Twardowski et al, has become an important research tool [3]. A simpler and less time-consuming version, called the "fast PET," exists, but this version is less popular due to several flaws [12].

CLINICAL APPLICATIONS — 

The PET has several clinical applications, particularly the classification of peritoneal membrane function and the assessment of inadequate dialysis (table 1) [13].

Another approach to assessing peritoneal membrane status is the Peritoneal Dialysis Capacity (PDC) test, which utilizes the following three parameters:

●An area parameter (A0/dX), which is equivalent to the dialysate to plasma (D/P) ratio for PET

●JvR, which is the fluid reabsorption rate after glucose equilibrium is achieved

●JvL, which is the large pore fluid flux

Although limited data suggest that the PDC test may help categorize the underlying cause of low ultrafiltration (UF) [14], further study is required to understand the possible role for this approach [15].

Timing of baseline test — A PET should be performed shortly after initiation of peritoneal dialysis to establish baseline values. The PET is then repeated when clinical problems arise and when clinical suspicion of an alteration in membrane transport occurs. This is in general agreement with the 2021 International Society for Peritoneal Dialysis guidelines [10].

The timing of the baseline PET varies by center. We perform a PET approximately one to two weeks after initiation of peritoneal dialysis therapy (which is three to four weeks after catheter insertion); in our experience, longer time intervals are unnecessary. However, some centers wait to perform the baseline PET for approximately four weeks after initiation of peritoneal dialysis due to a concern that peritoneal transport characteristics obtained before this time frame may be less accurate [16].

Peritoneal membrane function classification — The transport classifications for creatinine D/P and glucose D/D0 based upon averages, standard deviations, and minimal and maximum values over four hours are shown in the figure (figure 1). Drain volumes correlate positively with dialysate glucose and negatively with D/P creatinine at four-hour dwell times.

Peritoneal dialysis patients are classified as having one of the following peritoneal membrane function characteristics based upon the results of the PET:

●High transporter (or fast transporter) – Defined as a creatinine D/P greater than +1 standard deviation (SD) from the mean or a glucose D/Do of less than -1 SD from the mean

●Low transporter (or slow transporter) – Defined as a creatinine D/P of less than -1 SD from the mean or a glucose D/Do of greater than +1 SD from the mean

●Average transporter – Defined as a creatinine D/P and a glucose D/Do of between +1 SD and -1 SD around the mean

Almost 90 percent of properly conducted PETs show consistency in both ratios [17]. If there is discrepancy between the creatinine D/P and glucose D/D0, the test should be repeated. This discrepancy is often the result of elevated serum glucose levels. If serum glucose is elevated (>235 mg/dL), the classification should be based on D/P creatinine only [17].

The mean and standard deviation values for these ratios vary by center. However, after a four-hour dwell during a PET, a typical population of patients has a mean creatinine D/P ratio of approximately 0.65, and high transporters typically have a creatinine D/P ratio of >0.8. In the original series, approximately two-thirds of patients had average transport rates on the baseline PET [12]. The remaining one-third consisted almost equally of high and low transporters. This distribution, however, may not be observed in all patient populations [18].

Some experts do not categorize peritoneal solute transport (or transfer) using the schemata above [10]. This is because the creatinine D/P is a continuous variable with a normal distribution, which precludes the determination of absolute threshold values. For example, some patients classified as “average transporters” who have creatinine D/P in the higher range will have characteristics of high/fast solute transport. However, we find this classification of peritoneal membrane transport [3] to be simple, practical, and clinically useful; as such, we continue to use it while appreciating its limitations.

To emphasize that the movement of solutes across the peritoneal membrane occurs by passive diffusion rather than an active process, some experts have proposed replacing the term “transport” with “transfer” [10]. In such a schema, the term “fast transport” would be replaced by “fast solute transfer rate.” Although we believe this semantic change is reasonable, the term “transport” remains commonly used in clinical practice and therefore is used in this topic review.

There appears to be an association between initial peritoneal transport status and certain clinical features, particularly age. This was best studied in a report of 3188 patients from Australia and New Zealand who initiated peritoneal dialysis between 1991 and 2002 and underwent a baseline PET within the first six months [19]. Upon multivariate analysis, a high transporter was associated with increased age (odds ratio [OR] 1.08 for each 10 years, 95% CI 1.03-1.13) and ethnicity (OR 1.48 for Maori and Pacific Islander racial origin, 95% CI 1.13-1.94). By comparison, this finding was not associated with sex, diabetes and other comorbid conditions, smoking, previous hemodialysis therapy or transplantation, or residual kidney function. A similar association between increasing age and high-transporter status at dialysis initiation was noted in a second, smaller study from Spain [20].

Prediction of dialysis dose — The effective peritoneal dialysis dose is customarily measured by calculating the clearance of creatinine, which is the product of the D/P creatinine and the drain volume:

Solute clearance and UF vary with peritoneal membrane function:

●Low transporter – The solute D/P ratio increases almost linearly during a long-dwell exchange in a low transporter. In addition, the ultrafiltrate continues to be generated late during the dwell. Clearance per exchange therefore increases almost linearly throughout the long-dwell exchange (figure 2).

●High transporter – In high transporters, intraperitoneal volume begins to diminish after three to four hours since UF and solute equilibration peak early. The clearance per exchange begins to diminish beyond this time.

●Average transporter – Peak clearances for average transporters are attained for approximately between 8 to 10 hours.

Selection of peritoneal dialysis regimen — Since the features of clearance and filtration vary significantly with membrane function, the optimal peritoneal dialysis regimen will differ according to transporter type (algorithm 1). (See "Evaluating patients for chronic peritoneal dialysis and selection of modality".)

Solute concentration in the effluent during an exchange is derived by both diffusive and convective transport, as well as by dilution from free water movement across aquaporin.

●Low transporter – Because clearances continue to increase with time, low transporters are treated with long-dwell exchanges via continuous ambulatory peritoneal dialysis (CAPD) or continuous cyclic peritoneal dialysis (CCPD). Due to the slow rate of increase in the D/P ratio, clearance per unit time is augmented relatively little by rapid exchange techniques such as nightly intermittent peritoneal dialysis (NIPD).

●High transporter – The clearance per exchange over long dwell is less in patients with high transport rates. During the shorter dwell, high transporters capture maximum UF and completely equilibrate small solutes. These patients are therefore best treated with techniques using short-dwell exchanges, such as NIPD or daytime ambulatory peritoneal dialysis (DAPD). (See "Rapid transport (fast solute transfer) in peritoneal dialysis".)

●Average transporter – Patients with average transport rates can be effectively treated with either short- or long-dwell exchange techniques.

Long-term monitoring of membrane function — Changes in the D/P ratio have been used by a number of researchers to monitor peritoneal membrane function over time. Since PET results and clearances are highly reproducible, a change over time of a transport rate as assessed by an alteration in the D/P ratio should indicate a transport rate change. However, long-term studies on peritoneal membrane function in peritoneal dialysis patients have reported variable results [21-23]. One analysis primarily including ambulatory peritoneal dialysis (APD) patients has shown that the D/P creatinine ratio is a strong predictor of outcomes (mortality and hospitalization) [24].

Diagnosis of membrane injury — Although many patients with acute peritonitis display altered peritoneal membrane function, it is not customary to perform a PET during or after an episode of peritonitis, since acute changes are usually reversible after recovery [25,26]. However, many patients with acute peritonitis require a change in their dialysis prescriptions due to the increased transport of both large and small solutes and reduced drain volumes [27,28]. The change in prescription usually involves increasing the glucose tonicity or shortening the dwell time to obtain improved UF. A discussion concerning the effect of peritonitis on the dialysis prescription can be found elsewhere. (See "Rapid transport (fast solute transfer) in peritoneal dialysis".)

Some severe peritonitis episodes result in irreversible membrane changes due to extensive intra-abdominal adhesions; these adhesions compromise solute and water transport due to reduced membrane fluid contact [29]. In this setting, the PET will show a low D/P creatinine ratio and drain volume [29]. The diagnosis is confirmed by computed tomography (CT) scan with intraperitoneal contrast [30] or by infusion of an intraperitoneal radioisotope and peritoneal scintigraphy [31].

Diagnosis of causes of inadequate ultrafiltration and solute clearance — The following is an overview of the use of PET in assessing the causes of inadequate UF and/or solute clearance. A detailed discussion of these subjects are presented separately. (See "Management of hypervolemia in patients on peritoneal dialysis" and "Inadequate solute clearance in peritoneal dialysis".)

Any patient who requires three or more 4.25 percent glucose dialysis solution exchanges to maintain dry weight may have inadequate UF capacity. A UF volume less than 400 mL after a four-hour dwell with 2 L of 4.25 percent dextrose defines ultrafiltration insufficiency. The diagnostic importance of the PET in determining the causes of inadequate UF is shown in the algorithm (algorithm 2). In this algorithm, it is assumed that every patient has had a baseline PET performed early after initiation of peritoneal dialysis. (See 'Procedure' above.)

When a patient complains of fluid retention, the clinician should first ascertain that the drain volume is indeed reduced before performing another PET. Unchanged drain volume with fluid retention is seen with the loss of residual kidney function, excessive fluid intake, or noncompliance with the dialysis prescription.

If the drain volume is verifiably reduced, the clinician should repeat a PET, preferably with 4.25 percent dextrose (algorithm 2) [32]:

●When PET results are unaltered from the baseline values, UF insufficiency is due to either loss of dialysate outside the peritoneal cavity (excessive lymph absorption or dialysis solution leak into the abdominal wall or thoracic cavities) or failure to drain the dialysate because of catheter malfunction.

●When PET results suggest that membrane transport (solute clearance) has increased, bacterial or chemical peritonitis should be suspected. If peritonitis is absent, the constellation of inadequate UF and increased solute clearance is termed type I membrane dysfunction; this condition occurs in some patients in whom peritoneal dialysis has been continuous for prolonged periods and, as reported by some studies but not others, in some patients with frequent prior peritonitis episodes [33,34].

In type I membrane dysfunction, the inability to generate sufficient UF is gradual and permanent. Patients report using an increasing percentage of hypertonic solutions to maintain dry body weight. Cycler dialysis with short-dwell exchanges may occasionally restore fluid balance. In some, temporary cessation of peritoneal dialysis may transiently restore UF capacity and allow remesotheliazation [34]. In others, however, sclerosing peritonitis (see below) develops after the switch to hemodialysis [35]. (See "Rapid transport (fast solute transfer) in peritoneal dialysis".)

●Decreased solute and fluid removal with repeat PET is termed type II membrane dysfunction. This condition may be due to severe, recurrent, or smoldering peritonitis, extensive adhesions resulting from previously severe peritonitis, or an extremely rare disorder, sclerosing encapsulated peritonitis (SEP). SEP is a progressive condition, which continues to evolve even after cessation of peritoneal dialysis. Progressive intra-abdominal adhesions may eventually lead to intestinal obstruction and death [36].

Serial PET studies in proven cases of sclerosing peritonitis suggest that SEP goes through several phases. The initial phase is similar to type I membrane dysfunction (high-transport rates), which then progresses to type II membrane dysfunction [36]. If peritoneal dialysis is discontinued in a timely manner, the initial phase is reversible. (See "Inadequate solute clearance in peritoneal dialysis".)

Diagnosis of early ultrafiltration insufficiency — We do not routinely obtain sodium dialysate measurements in the evaluation of decreased UF, since a PET without such measurements usually provides sufficient information. However, some experts measure the one-hour dialysate sodium during PET to assess UF [10]. In normal patients, the sodium D/P curve typically exhibits an initial drop due to the high rate of UF. Because of sodium sieving, the UF is initially low in sodium. With the cessation of UF later during the dwell, dialysate sodium tends to equilibrate with that of capillary blood, thereby returning the D/P sodium to baseline. Absence of the initial drop of D/P sodium is therefore an indication of UF insufficiency, a finding typically observed in the early phase of SEP [37].

The dip in dialysate sodium maximizes between one to two hours of dwell. When using a 4.25 percent dextrose PET, a sodium dip ≤5 mmol/L and/or a sodium sieving ratio ≤0.03 at one hour indicates UF insufficiency [10]. UF insufficiency, if present at the time of start of peritoneal dialysis, is due to a disorder of free water transport as well as small-pore UF. Improvement in UF insufficiency in such patients is linked to improvement in small pore-mediated water transport [38].

Assessing the influence of systemic disease on peritoneal membrane function — Several reports have indicated conflicting peritoneal membrane patterns for certain systemic diseases, such as diabetes mellitus, systemic sclerosis, systemic lupus erythematosus, and amyloidosis.

SUMMARY AND RECOMMENDATIONS

●General principles – The peritoneal equilibration test (PET) is a semiquantitative assessment of peritoneal membrane transport function in patients on peritoneal dialysis. The ratio of solute concentrations in dialysate and plasma (D/P ratio) at specific times (t) during the dwell signifies the extent of solute equilibration. (See 'Introduction' above.)

●PET procedure – The PET is a highly reproducible procedure consisting of a standardized four-hour dialysis exchange with a dialysis solution. The standardized test measures dialysate creatinine and glucose levels at zero, two, and four hours of dwell and serum levels of creatinine and glucose at any time during the test. (See 'Elements of the peritoneal equilibration test' above.)

●Clinical applications – The PET has a number of clinical applications. It is principally used to classify peritoneal membrane function and assess the reasons possibly underlying inadequate dialysis or ultrafiltration (UF). It is not customary to perform a PET during or after an episode of peritonitis, since acute changes are usually reversible after recovery. (See 'Clinical applications' above and "Inadequate solute clearance in peritoneal dialysis" and "Management of hypervolemia in patients on peritoneal dialysis".)