Understanding Testing Methods

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Patient treatment success in PD is dependent on the functional and morphological integrity of the peritoneal membrane.  Besides functional failure of the peritoneum, long-term PD may lead to anatomic changes in the peritoneal tissues such as neoangiogenesis, vasculopathy and fibrosis, sometimes causing peritoneal sclerosis.  Because of these changes peritoneal permeability varies widely between patients and can change significantly over time within an individual.  The peritoneal membrane changes, and as a consequence the peritoneal transport status, have been reported to play a major role in determining patients’ morbidity and mortality¹.  In order to find an appropriate PD modality and prescription it is crucial to assess the actual peritoneal membrane transport status as accurately as possible.  Peritoneal membrane transport does not only refer to transport of solutes, e.g. uremic toxins and electrolytes, but also to fluid transport.  Since both elimination of uremic toxins and ultrafiltration account for adequacy, it is important that a test reliably assesses both parameters. 

Understanding the testing methods

Numerous techniques for measuring peritoneal transport are available.

The PET (peritoneal equilibration test) was the first standardized method to quantify individual peritoneal membrane characteristics and to compare the individual results with larger populations².  It requires the collection of peritoneal effluent samples at time intervals over four hours using a standard protocol and a mid-point blood sample as outlined in the Clinical procedure for PET.  The results are expressed as dialysate to plasma ratios (D/P) for the specific times for urea, creatinine and sodium or as dialysate dextrose concentration (D_t) at a certain time over dialysate dextrose concentration at time zero (D₀) or immediately after infusion.  The results are plotted as D/P or D_t/D₀ versus time in hours.  The values are categorized as high-average, high, low-average and low by using the mean of a large population + 1 and + 2 SD.  The PET has been serially repeated and found to be stable and reproducible over time. However, it is imperative to follow the test protocol rigorously in order to achieve reproducibility. 

Since the PET is very labor intensive, a modified or fast PET³ was designed to simplify the procedure, reduce cost and improve compliance with testing.  It requires only one dialysate sample, eliminates the supervised inflow procedure, the baseline and two hour measurements and substitutes dialysate glucose at 4 hours for the ratio of the 4 hour value to baseline glucose dialysate value (D₄/D₀).  The results of this single dialysate sample are interpreted using a standard table that classifies the data by transport categories.  The main limitations of the fast PET are the lack of internal controls and reproducibility Clinical procedure for fast PET. 

The original PET was standardized for a long overnight exchange since almost all patients were on CAPD and this was the most convenient approach.  Recent studies confirmed the minimal impact of the prior long exchange on small solute equilibration.  Thus, for clinical purposes, Twardowski, et al. introduced the short PET⁴ accepting any dwell time between 3 and 12 hours for the prior exchange and simplifying the test to include either a 2 or 4 hour dwell. Gotch, et al. have suggested that the procedural steps in the PET may actually overestimate peritoneal membrane transport and underestimate the variation in peritoneal transport that may occur under actual clinical conditions⁵.  Moreover, it is imperative to be aware that the PET alone does not give an assessment of total solute removal (adequacy).  Thus, the PET should be combined with a 24-hour collection for renal and peritoneal solute clearance.

The Peritoneal Function Test (PFT), developed by Gotch, et al. has been extensively used and validated in multicenter studies^6,7. The test allows assessment of total delivered therapy for urea and creatinine, protein and calorie nutrition, fluid balance, and peritoneal transport.  Clinical procedure for PFT.  The results are expressed as Pt₅₀ or the time required for a solute to achieve 50% equilibration between dialysate and plasma.  The PFT has been extensively used as part of a kinetic modeling program (Pack-PD^® or Patient on-line [POL]) and the data can be displayed for individual patients, clinics or regional groups of dialysis centers. 

For follow up, a simplified PFT (SPFT) can be used. Clinical procedure for simplified PFT

The 24-hour batch dialysate test in combination with a simultaneous urine collection and a blood sample can provide a good measure of delivered dialysis dose^8,9.  Clinical procedure for 24-hour batch dialysate test. The main disadvantage is the required collection of individual drains and their measurement.  Unless the patient is well trained and reliable, it is best to perform the measurements and sampling at the clinic.  According to one study, the 24-hr D/P_creatinine correlates well with the PET transport information⁹.

The peritoneal dialysis capacity (PDC) program was designed to measure transperitoneal passage of fluid and solutes under normal conditions with a non-invasive test.  The PDC is based on the three-pore-model of Rippe, et al^10,11.  It describes the peritoneal membrane characteristics by means of three parameters: 1) the area parameter A_0/DX, which determines the diffusion of small solutes; 2) the final reabsorption rate of fluid from the abdominal cavity to blood when the glucose gradient has dissipated (Jv_AR); and 3) the large pore fluid flux (JV_L) which determines the loss of protein to the PD fluid.  The PDC parameters are highly reproducible and the program can be used to achieve adequate dialysis and better understanding of the dynamics of PD exchanges. For the specific procedure protocol see reference 12. 

The dialysis adequacy and transport test (DATT) was introduced by Rocco et al. in an attempt to develop an easier test for classifying peritoneal transport type^13,14.  Only a serum sample and a 10 ml aliquot from a pooled, well-mixed 24-hour dialysate are required for the calculation of the 24-hour D/P. Since the DATT has only been validated for patients on a fixed CAPD schedule of 4 two-liter exchanges, this test should only be used for patients on this prescription and should not be used for patients on cycler therapy¹⁵.

The accelerated peritoneal examination (APEX) test was designed by Verger et al. using a similar protocol as their initial equilibration test with 3.86% glucose solution, but summarizes in a single number the peritoneal permeability for both glucose and urea¹⁶.  It represents the time at which the glucose and urea equilibration curves cross.  Generally, the APEX may be shorter than a PET since most patients exhibit a crossing of the curves before 2 hours.  The shorter the APEX time, the higher the peritoneal permeability and, conversely, the longer the time, the lower the peritoneal permeability.  The APEX time may help to define the optimum contact time between the functional peritoneal membrane surface area and the dialysate for the individual patient.  If UF is the major goal, short dwell times should be used.  If solute clearance is the major goal, longer dwell times should be used.

The standard peritoneal permeability analysis (SPA) is a more sophisticated way to assess peritoneal function¹⁷.  It uses intraperitoneally administered dextran 70 to study fluid kinetics during a 4-hour dwell using an infusion volume consistent with the patient’s usual prescription.  The study is performed at the center over a period of 4 hours and requires two blood samples and many timed peritoneal effluent samples.  The SPA is useful in assessing MTAC of small solutes, clearance of proteins and changes in IP volume.   

For each test mentioned above it has to be considered that peritoneal transport characteristics change significantly within the first month of PD. Peritoneal function tests performed during this time should be seen as preliminary and should be confirmed by an additional test 4 weeks later¹⁸.  It is also important to recognize that peritoneal membrane function measurement - no matter if solute clearance or UF – is subject to error.  Therefore, one should be cautious with the interpretation of a single reading. 

Possible differences in peritoneal transport between children and adults have been discussed by many authors.  A recent study by Bouts, et al. did not confirm these concerns¹⁹.  The results suggest that the peritoneal membrane in children may not be different from that in adults.  Generally, all the tests mentioned above are also applicable in children using the appropriate exchange volume. 

It is unclear how often peritoneal function should be assessed.  The KDOQI guidelines recommend a measurement every 4 months²⁰.  However, the tests are time-consuming for both patients and nurses and costly.  Ideally, one standard test used worldwide would be advisable, but since each test presently applied has its pros and cons, it is up to the Medical Director, which test best fits their needs.

References:

1. Churchill DN, Thorpe KE, Nolph KD, et al. Increased peritoneal membrane transport is associated with decreased patient and technique survival for continuous peritoneal dialysis patients. The Canada-USA (CANUSA) Peritoneal Dialysis Study Group. J Am Soc Nephrol 9:1285-1292, 1998
2. Twardowski ZJ, Nolph KD, Khanna R, et al. Peritoneal equilibration test. Perit Dial Bull 7:138-47, 1987
3. Twardowski ZJ. PET--a simpler approach for determining prescriptions for adequate dialysis therapy. Adv Perit Dial 6:186-191, 1990
4. Twardowski ZJ, Prowant BF, Moore HL, et al. Short peritoneal equilibration test: impact of preceding dwell time. Adv Perit Dial 19:53-58, 2003
5. Gotch F, Schoenfeld PY, Gentile DE.  The peritoneal equilibration test (PET) is not a realistic measure of peritoneal clearance (PC). J Am Soc Nephrol 2:361, 1991 (Abstract)
6. Gotch FA and Keen ML. Kinetic modelling in peritoneal dialysis. In: Nissenson AR, Fine RN, Gentile DE, and Eds. Clinical Dialysis, 3rd edition Norwalk CT: Appleton & Lange, 1995: 343-375
7. Gotch FA, Lipps BJ, Keen ML, Panlilio F. Computerized urea kinetic modeling to prescribe and monitor delivered Kt/V (pKt/V, dKt/V) in peritoneal dialysis. Adv Perit Dial 12:43-45, 1996
8. Mooraki A , Kliger A, Gorban-Brennan NL, et al. Weekly Kt/V urea and selected outcome criteria in 56 randomly selected CAPD patients. Adv Perit Dial 9:92-96, 1993
9. Busch S, Schreiber M, Bodnar D, et al. The 24-hour D/P ratio is a convenient screen for identifying altered peritoneal transport rates. Adv Perit Dial 9:119-123, 1993
10. Haraldsson B. Assessing the peritoneal dialysis capacities of individual patients. Kidney Int 47:1187-1198, 1995
11. Rippe B, Stelin G, Haraldsson B. Computer simulations of peritoneal fluid transport in CAPD. Kidney Int 40:315-325, 1991
12. Van Biesen W, Carlsson O, Bergia R, et al. Personal dialysis capacity (PDCTM) test: a multicentre clinical study. Nephrol Dial Transplant 18:788-796, 2003
13. Rocco MV, Jordan JR, Burkart JM. Determination of peritoneal transport characteristics with 24-hour dialysate collections:  Dialysis adequacy and transport test. J Am Soc Nephrol 5:1333-1338, 1994
14. Rocco MV, Jordan JR, Burkart JM. 24-hour dialysate collection for determination of peritoneal membrane transport characteristics: Longitudinal follow-up data for the dialysis adequacy and transport test (DATT). Perit Dial Int 16:590-593, 1996
15. Paniagua R, Amato D, Correa-Rotter R, et al. Correlation between peritoneal equilabration test and dialysis adequacy and transport test, for peritoneal transport type characterization. Perit Dial Int 20:53-59, 2000
16. Verger C, Larpent L, Veniez G, et al. L'APEX...description et utilisation. Bull Dial Perit 1:36-40, 1991
17. Panneekeet MM, Imholz ALT, Koomen GCM, et al.  The standard peritoneal permeability analysis: A tool for the assessment of peritoneal permeability characteristics in CAPD patients. Kidney Int 48:466, 1995
18. Johnson DW, Mudge DW, Blizzard S, et al. A comparison of peritoneal equilibration tests performed 1 and 4 weeks after PD commencement. Perit Dial Int 24:460-465, 2004
19. Bouts AH, Davin JC, Groothoff JW, et al. Standard peritoneal permeability analysis in children. J Am Soc Nephrol 11:943-950, 2000
20. National Kidney Foundation. K/DOQI Clinical practice guidelines for peritoneal dialysis adequacy, 2000. Am J Kidney Disease 37(Suppl 1):S65-136, 2001