Understanding Testing Methods

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 anatomical changes in the peritoneal tissues such as neoangiogenesis, vasculopathy and fibrosis, sometimes causing peritoneal sclerosis. Due to these changes, peritoneal permeability varies widely between patients and can change significantly over time within an individual. Changes in the peritoneal membrane resulting in increased peritoneal transport status reportedly 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 contribute to adequate dialysis, it is important that a test reliably assesses both parameters.

Understanding the testing methods

Numerous techniques for measuring peritoneal transport are available.

 

Parameters measured

PET

PFT

PDC

24-hour batch

DATT

APEX

SPA

Peritoneal membrane transport

X

X

X

X

X

X

Total peritoneal clearance

X

X

X

Residual renal function

X

X

X

Ultrafiltration

X

X

X

X

X

Nutritional status

X

X

X

 

The peritoneal equilibration test (PET) 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 ( Clinical procedure for PET.pdf). The results are expressed as the dialysate to plasma ratio (D/P) for urea, creatinine, or sodium. For glucose, the results are expressed as the ratio of the dialysate dextrose concentration (Dt) at a certain time over dialysate dextrose concentration at time zero (D0). The result allows the patient to be categorized as high, high-average, average, low-average, or low based on the mean values of a large population (+1 and +2 SD)2,3. 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 PET4 was designed to simplify the procedure, reduce cost, and improve compliance with testing ( Clinical procedure for fast PET.pdf)

 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.

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 PET5 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 conditions6. Moreover, it is important 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 studies7,8. 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.pdf). 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 and the data can be displayed for individual patients, clinics, or regional groups of dialysis centers9.

For follow up, a simplified PFT (SPFT)10 can be used ( Clinical procedure for simplified PFT.pdf).

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 dose11,12 ( Clinical procedure for 24-hour batch dialysate test.pdf). 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. In addition, this test does not provide information on membrane transport characteristics. Although, one study demonstrated that the 24-hr D/Pcreatinine data correlates well with extrapolated PET data12. Thus, alterations from expected D/P ratios could suggest possible changes in membrane characteristics.

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 al13,14. It describes the peritoneal membrane characteristics by means of three parameters: 1) the area parameter A0/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 (JvAR); and 3) the large pore fluid flux (JVL), 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. Van Biesen et al. outline a specific procedure protocol14.

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 type15,16. 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 therapy17.

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 urea18. 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 APEX time indicates higher peritoneal permeability and, conversely, the longer time is indicative of lower peritoneal permeability. The APEX time may help to define the optimum contact (dwell) time between the functional peritoneal membrane surface area and the dialysate for the individual patient. If ultrafiltration 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 function3. 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 (mass transfer-area coefficient) of small solutes, clearance of proteins, and changes in ultrafiltration volume.

For each test mentioned above, the fact that transport characteristics change significantly within the first month of PD has to be considered. Peritoneal function tests performed during this time should be seen as preliminary and should be confirmed by an additional test 4 weeks later19. It is also important to recognize that peritoneal membrane function measurement, solute clearance and/or ultrafiltration, 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 concerns20. 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.

Regarding testing frequency, the KDOQI guidelines recommend peritoneal membrane function testing when clinically indicated, such as during unexplained volume overload, decreasing drain volume, increased need for hypertonic solutions, worsening hypertension, changes in Kt/Vurea, and unexplained uremic symptoms21. All measurements of peritoneal transport characteristics should be obtained when the patient is clinically stable and at least 1 month after resolution of an episode of peritonitis.

References:

  1. Churchill DN, Thorpe KE, Nolph KD, Keshaviah PR, Oreopoulos DG, Pagé D. Increased peritonealmembrane 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. 1998;9(7):1285-92. www.ncbi.nlm.nih.gov/pubmed/9644640
  2. Twardowski Z j., Nolph KO, Khanna R, Prowant BF, Ryan LP, Moore HL, Nielsen MP. Peritoneal Equilibration Test. Perit Dial Int. 1987;7(3):138-148.
  3. Pannekeet MM, Imholz AL, Struijk DG, Koomen GC, Langedijk MJ, Schouten N, de Waart R, Hiralall J, Krediet RT. The standard peritoneal permeability analysis: a tool for the assessment of peritoneal permeability characteristics in CAPD patients. Kidney Int. 1995;48(3):866-75. www.ncbi.nlm.nih.gov/pubmed/7474677
  4. Twardowski ZJ. PET–a simpler approach for determining prescriptions for adequate dialysis therapy. Adv Perit Dial. 1990;6:186-91. www.ncbi.nlm.nih.gov/pubmed/1982805
  5. Twardowski ZJ, Prowant BF, Moore HL, Lou LC, White E, Farris K. Short peritoneal equilibration test: impact of preceding dwell time. Adv Perit Dial. 2003;19:53-8. www.ncbi.nlm.nih.gov/pubmed/14763034
  6. Gotch F, Schoenfeld P, Gentile D. The peritoneal equilibration test (PET) is not a realistic measure of peritoneal clearance (PC). (Abstract). In: 24th annual meeting of the American Society of Nephrology (ASN). November 17-20, 1991.Vol 2. J Am Soc Nephrol; 1991:231-822.
  7. Gotch FA, Keen ML. Kinetic Modeling in Peritoneal Dialysis. In: Nissenson AR, Fine RN, eds. Clinical Dialysis. 4th ed. New York: McGraw-Hill Medical Publication; 2005:385-420.
  8. 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. Fresenius Randomized Dialysis Prescriptions and Clinical Outcome Study (RDP/CO). Adv Perit Dial. 1996;12:43-5. www.ncbi.nlm.nih.gov/pubmed/8865870
  9. Gotch FA, Lipps BJ. PACK PD: a urea kinetic modeling computer program for peritoneal dialysis. Perit Dial Int. 1997;17 Suppl 2:S126-30. www.ncbi.nlm.nih.gov/pubmed/9163812
  10. Selçuk NY, Tonbul HZ, Capoğlu I, San A. Simplified peritoneal equilibration test in CAPD. Nephron. 1998;80(1):109-10. www.ncbi.nlm.nih.gov/pubmed/9730726
  11. Mooraki A, Kliger AS, Gorban-Brennan NL, Juergensen P, Brown E, Finkelstein FO. Weekly KT/V urea and selected outcome criteria in 56 randomly selected CAPD patients. Adv Perit Dial. 1993;9:92-6. www.ncbi.nlm.nih.gov/pubmed/8105972
  12. Busch S, Schreiber M, Bodnar D, Buchler N, Fuchs J, Jackson-Bey D, Pearl J. The 24-hour D/P ratio is a convenient screen for identifying altered peritoneal transport rates. Adv Perit Dial. 1993;9:119-23. www.ncbi.nlm.nih.gov/pubmed/8105903
  13. Rippe B, Stelin G, Haraldsson B. Computer simulations of peritoneal fluid transport in CAPD. Kidney Int. 1991;40(2):315-25. www.ncbi.nlm.nih.gov/pubmed/1942781
  14. Van Biesen W, Carlsson O, Bergia R, Brauner M, Christensson A, Genestier S, Haag-Weber M, Heaf J, Joffe P, Johansson A-C, Morel B, Prischl F, Verbeelen D, Vychytil A. Personal dialysis capacity (PDC(TM)) test: a multicentre clinical study. Nephrol Dial Transplant. 2003;18(4):788-96. www.ncbi.nlm.nih.gov/pubmed/12637650
  15. Rocco M V, Jordan JR, Burkart JM. Determination of peritoneal transport characteristics with 24-hour dialysate collections: dialysis adequacy and transport test. J Am Soc Nephrol. 1994;5(6):1333-8. www.ncbi.nlm.nih.gov/pubmed/7893998
  16. Rocco M V, 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. 1996;16(6):590-3. www.ncbi.nlm.nih.gov/pubmed/8981526
  17. Paniagua R, Amato D, Correa-Rotter R, Ramos A, Vonesh EF, Mujais SK. Correlation between peritoneal equilibration test and dialysis adequacy and transport test, for peritoneal transport type characterization. Mexican Nephrology Collaborative Study Group. Perit Dial Int. 2000;20(1):53-9. www.ncbi.nlm.nih.gov/pubmed/10716584
  18. Verger C, Larpent L, Veniez G, Brunetot N, Corvaisier B. L’APEX… description et utilisation [French]. Bull Dial Perit. 1991;1:36-40.
  19. Johnson DW, Mudge DW, Blizzard S, Arndt M, O’Shea A, Watt R, Hamilton J, Cottingham S, Isbel NM, Hawley CM. A comparison of peritoneal equilibration tests performed 1 and 4 weeks after PD commencement. Perit Dial Int. 2004;24(5):460-5. www.ncbi.nlm.nih.gov/pubmed/15490986
  20. Bouts AH, Davin JC, Groothoff JW, Van Amstel SP, Zweers MM, Krediet RT. Standard peritoneal permeability analysis in children. J Am Soc Nephrol. 2000;11(5):943-50. www.ncbi.nlm.nih.gov/pubmed/10770974
  21. K/DOQI Clinical practice guidelines for peritoneal adequacy, update 2006. Am J Kidney Dis. 2006;48 Suppl 1:S91-7. www.ncbi.nlm.nih.gov/pubmed/16813997

P/N 102480-01 Rev. A 12/2014