The peritoneal equilibration test (PET) was developed THE SHORT PET IN PEDIATRICS. Bradley A. Warady and Janelle Jennings

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1 Peritoneal Dialysis International, Vol. 27, pp Printed in Canada. All rights reserved /07 $ Copyright 2007 International Society for Peritoneal Dialysis THE SHORT PET IN PEDIATRICS Bradley A. Warady and Janelle Jennings Children s Mercy Hospitals and Clinics, Kansas City, Missouri, USA Background: The peritoneal equilibration test (PET) is a 4-hour procedure that is recommended to be performed in children receiving peritoneal dialysis to assist in prescription management. While a shortened version of the PET has been used in adults and reliably characterizes peritoneal membrane transport capacity, no similar experience with children has been reported. Methods: Retrospective evaluation of 2-hour and 4-hour PET data obtained from 20 children receiving chronic peritoneal dialysis in a single center. Characterization of membrane transport capacity was based on evaluation of serum and dialysate samples used to determine the dialysate-toplasma ratio (D/P) of creatinine and the ratio of dialysate to baseline dialysate ( ). Patient values were compared to pediatric reference data. Results: In all 20 patients, characterization of peritoneal membrane transport capacity using 2-hour D/P and results was identical to that determined using 4-hour data for the same solute. While the creatinine- and based characterization was discrepant in 14 of 20 patients, in only 1 case was the discrepancy of more than a single transport category. Conclusion: These results support the accuracy of a short PET in children, a procedure that should prove beneficial in terms of patient and staff time. Perit Dial Int 2007; 27: KEY WORDS: Peritoneal equilibration test; pediatric. The peritoneal equilibration test (PET) was developed by Twardowski as a clinically useful means of characterizing peritoneal membrane transport capacity in patients receiving peritoneal dialysis (PD) (1). Determination of the dialysate-to-plasma ratio (D/P) of creatinine and the ratio of dialysate to baseline dialysate ( ) on several occasions over the Correspondence to: B.A. Warady, Children s Mercy Hospitals and Clinics, 2401 Gillham Road, Kansas City, Missouri, USA. bwarady@cmh.edu Received 30 October 2006; accepted 6 February course of a 4-hour test provides data that can be used to assist in PD prescription management. Reference PET data based on studies conducted in adults and children are available, and performance of the test is recommended in the current K/DOQI PD adequacy guidelines (1 4). The somewhat labor-intensive nature of the PET evaluation prompted the development of two modifications of the procedure by Twardowski et al. The fast PET requires only a single sample of dialysate and blood 4 hours after the infusion of the test exchange volume, whereas the short PET, a modification described in the original PET publication, requires determination of D/P and ratios after a 2-hour equilibration time, in contrast to the standard 4-hour time period (1,5,6). The desirability of a procedure that could be completed in 2 hours and the lack of data in children similar to that collected in adults, prompted us to review PET data from our patients to determine the accuracy of data obtained at 2 hours as a means of characterizing peritoneal membrane transport capacity in children receiving chronic PD. PATIENTS AND METHODS The PET data of 20 consecutive patients receiving automated PD was retrospectively reviewed following institutional review board approval. In each case, the study was performed within the initial 8 months of dialysis and none of the patients had a history of peritonitis. A 4-hour PET was conducted on each patient. The test exchange fill volume was 1100 ml/m 2 body surface area (BSA) and the dialysate solution was 2.5% Dianeal (Baxter Healthcare, Deerfield, Illinois, USA). The method of DuBois and DuBois was used to determine BSA (7). During the evening prior to the PET, each patient received a 40 ml/kg exchange (range ml/kg) of 2.5% Dianeal, with a dwell time of 8 12 hours. After arrival at the dialysis unit on the day of testing, the overnight dwell was drained. A transfer set change to a Y-type Dianeal PD solution administration set was then conducted to minimize tubing dead space or recirculating 441

2 WARADY and JENNINGS JULY 2007 VOL. 27, NO. 4 PDI volume. The test exchange was conducted next and was infused over 10 minutes with the patient remaining supine and gently rolling side to side during the infusion. Dialysate samples were taken from the overnight exchange bag and from the patient, while supine, at 0, 30, 60, 120, 180, and 240 minutes of dwell time from the test exchange volume. Blood samples were obtained at 0, 120, and 240 minutes. All serum and dialysate samples were analyzed for creatinine and on a Kodak Ektachem 700 machine (Eastman Kodak, Rochester, New York, USA). The Ektachem uses an enzymatic assay that has no interference with. The D/P ratios for creatinine at 2 hours and 4 hours of the PET were determined by using the plasma concentration of creatinine in the denominator, with the numerator consisting of the dialysate creatinine concentration. The ratios for were calculated at the same time points by dividing the dialysate concentrations at 2 hours and 4 hours by the initial dialysate concentration. To characterize peritoneal membrane transport capacity, the results of the PET assessment (D/P creatinine and ) were plotted on the reference curves published by Warady et al. (2) that are incorporated within PD Adequest (Baxter). Transport capacity at 2 hours and 4 hours of the test was categorized as low, low average, high average, or high. Based on the population reference data, a low transport capacity is defined by a D/P ratio below mean 1 standard deviation (SD), or a above mean + 1 SD. Low-average transport is defined by a D/P ratio between mean 1 SD and the mean, or a between the mean and mean + 1 SD. High average transport is defined by a D/P ratio between the mean and mean + 1 SD, or a between mean 1 SD and the mean. High transport is defined by a D/P ratio above mean + 1 SD or a below mean 1 SD. STATISTICAL ANALYSIS Values are presented as mean ± SD. Statistical analysis was performed using SPSS 12 (version 12.0; SPSS Inc., Chicago, Illinois, USA) for Windows operating system (Microsoft, Redmond, Washington, USA). Associations between the 2-hour and 4-hour D/P creatinine and values respectively were assessed by Pearson correlation analysis. A p value 0.05 was considered statistically significant. RESULTS At the time of dialysis initiation, the 20 patients (11 males) had a mean age of ± 72.6 months. 442 They had received dialysis for 4.15 ± 1.92 months (Table 1) at the time the PET evaluations were conducted. All patients received automated PD, with a prescription of 6 14 nightly exchanges with a single nocturnal exchange volume of ml/m 2 / BSA and a single daytime exchange volume that was 50% of the nocturnal volume. Characterization of the peritoneal membrane transport capacity of each patient based on the 2- and 4-hour D/P creatinine and the 2- and 4-hour values are described in Table 2. In all patients, the 2-hour and 4-hour solute transport data resulted in identical characterization of the membrane transport capacity when referenced to the same solute. However, discrepancies in the results existed in 14 cases when comparing creatinine- and -based data. In all but 1 of the 20 cases (Patient 14), the discrepancies were of a single transport category and thus fell within 1 SD of the reference population results. The 2-hour and 4-hour values for D/P creatinine and respectively were highly correlated (Figures 1 and 2). Based on the D/P creatinine data, the numbers of patients within each transport category were as follows: high, 3; high average, 6; low average, 8; low, 3. The mean D/P creatinine values by transport category obtained at 2 and 4 hours are described in Table 3. TABLE 1 Patient Population Patient Gender Age Dialysis duration 1 M 6 years, 4 months 2 months, 10 days 2 M 17 years, 5 months 7 months, 8 days 3 F 16 years, 4 months 2½ months 4 F 11 years, 5 months 4 months 5 F 4 years, 6 months 3½ months 6 M 5 years, 3 months 4 months 7 M 5 months 3 months 8 M 7 years, 4 months 2 months, 0 days 9 M 16 years, 4 months 2 months 10 M 10 years, 2 months 2 months, 7 days 11 M 1 month 7 months 12 F 14 years, 3 months 2½ months 13 M 10 years, 2 months 2 months, 5 days 14 F 1 year, 10 months 6 months 15 F 6 months 2½ months 16 F 10 months 6 months 17 F 13 years, 1 month 4 months 18 M 15 years, 3 months 3 months 19 M 1 month 8 months 20 F 8 years, 10 months 5 months Mean±SD 91.45±72.6 months 4.15±1.92 months

3 PDI JULY 2007 VOL. 27, NO. 4 THE SHORT PET IN PEDIATRICS TABLE 2 Peritoneal Membrane Transport Capacity D/P creatinine Patient 2-Hour 4-Hour 2-Hour 4-Hour 1 HA HA HA HA 2 L L LA LA 3 L L LA LA 4 L L LA LA 5 HA HA H H 6 LA LA HA HA 7 L L LA LA 8 HA HA HA HA 9 L L LA LA 10 L L LA LA 11 HA HA H H 12 L L L L 13 L L L L 14 L L HA HA 15 LA LA HA HA 16 LA LA HA HA 17 L L L L 18 L L LA LA 19 L L LA LA 20 H H H H = ratio of dialysate to baseline dialysate ; D/P = dialysate-to-plasma ratio; HA = high average; L = low; LA = low average; H = high. Figure 2 Correlation between 2-hour and 4-hour values in 20 children undergoing a peritoneal equilibration test. = ratio of dialysate to baseline dialysate. Based on the data, the numbers of patients within each transport category were as follows: high, 1; high average, 4; low average, 3; low, 12. The mean values by transport category obtained at 2 and 4 hours are described in Table 4. TABLE 3 Mean±SD D/P Creatinine Values 2-Hour D/P creatinine 4-Hour D/P creatinine H 0.71± ±0.05 HA 0.53± ±0.65 LA 0.43± ±0.04 L 0.38± ±0.05 D/P = dialysate-to-plasma ratio; H = high; HA = high average; LA = low average; L = low. TABLE 4 Mean±SD Glucose Values 2-Hour 4-Hour Figure 1 Correlation between 2-hour and 4-hour D/P creatinine values in 20 children undergoing a peritoneal equilibration test. D/P = dialysate-to-plasma ratio. H HA 0.44± ±0.04 LA 0.60± ±0.04 L 0.78± ±0.13 = ratio of dialysate to baseline dialysate ; H = high; HA = high average; LA = low average; L = low. 443

4 WARADY and JENNINGS JULY 2007 VOL. 27, NO. 4 PDI DISCUSSION 444 This retrospective study provides preliminary evidence that the PET results obtained at 2 hours and 4 hours, based on either creatinine or transport, in children who have recently initiated PD, who have been peritonitis free, and who conducted the PET with an 1100 ml/m 2 test exchange volume of 2.5% dextrose dialysis solution, provides identical characterization of peritoneal membrane transport capacity for the same solute (2). This suggests that, like the short PET in adults, a short version of the PET can also be applied to the pediatric population. The benefits of a 2-hour versus a 4-hour evaluation are many and include the fact that it is more convenient for patients, families, and nursing staff. In addition, the shorter evaluation is associated with cost savings related to the need for less staff time and equipment. Finally, and most importantly, the fewer obstacles that exist to the performance of the test make it likely that the evaluation will be carried out on a more routine basis, with a resulting improvement in patient care. Of particular interest is the fact that, in a substantial number of cases, categorization of membrane transport capacity based on and creatinine kinetics provided discrepant results, a finding previously noted by Twardowski et al. (5). However, in all but one of the cases in which there were discrepancies, they fell within 1 SD of the reference population results and thus are likely to be of limited clinical significance. Since creatinine transport rates tend to demonstrate the best correlation with adult patients clinical response to PD, consideration should be given to the preferential use of 2-hour D/P creatinine data to categorize membrane transport capacity in children. In contrast to the adult experience, the PET in children should routinely be performed with an exchange volume scaled to BSA, as was done with our patients, because of the direct relationship that exists between peritoneal surface area and BSA in children. The provision of a relatively small exchange volume results in rapid dissolution of the solute concentration gradient and the artifactual appearance of a rapid transport capacity (8). This may, in part, explain the greater percentage of patients we found with evidence of low/low average transport capacity compared to other recently published pediatric data (9). Whereas the reference data that we used were based on PET studies conducted with a test exchange volume of 1100 ml/m 2, near identical results for the PET have been obtained from children in Europe studied with an exchange volume of 1000 ml/m 2 (3). Historically, it has been recommended that an 8- to 12-hour exchange precede the PET, as was also performed with all of our patients. When the impact of the prolonged exchange on test results was formerly studied in adults, it was determined that any dwell time between 3 and 12 hours preceding the PET is acceptable and will not alter the study results (5). Unlike the situation with and creatinine, however, the length of the dwell time during the night before the PET has been shown to influence protein transport data. Since the movement of protein from blood to the peritoneal cavity is slow, the longer the exchange preceding the PET, the higher the concentration of protein in the residual peritoneal volume, and the higher the D/P protein ratio. Similar studies have not been conducted with pediatric patients. While it is recommended that all pediatric patients be evaluated with a PET soon after initiation of PD, in many centers only those patients whose course has been complicated by events that may have altered the membrane transport capacity (e.g., repeated peritonitis) regularly have a follow-up PET evaluation. Whether or not the short PET will accurately characterize membrane transport capacity in this setting will require further study. In summary, these preliminary data suggest that the short PET is a valid means of assessing peritoneal membrane transport capacity in children. Since the number of patients who have been evaluated with this procedure is small, additional studies with a larger group of patients should be encouraged. Only after such studies confirm the present results can the short PET be routinely recommended as part of the initial evaluation of children receiving peritoneal dialysis. REFERENCES 1. Twardowski ZJ, Nolph KD, Khanna R, Prowant BF, Ryan LP, Moore HL, et al. Peritoneal equilibration test. Perit Dial Bull 1987; 7: Warady BA, Alexander SR, Hossli S, Vonesh E, Geary D, Watkins S, et al. Peritoneal membrane transport function in children receiving long-term dialysis. J Am Soc Nephrol 1996; 7: Schaefer F, Langebeck D, Heckert KH, Scharer K, Mehls O. Evaluation of peritoneal solute transfer by the peritoneal equilibration test in children. Adv Perit Dial 1992; 8: National Kidney Foundation. KDOQI clinical practice guidelines and clinical practice recommendations for 2006 updates: hemodialysis adequacy, peritoneal dialysis adequacy and vascular access. Am J Kidney Dis 2006; 48(Suppl 1):S Twardowski ZJ. The fast peritoneal equilibration test. Semin Dial 1990; 3: Twardowski ZJ, Prowant BF, Moore HL, Lou LC, White E,

5 PDI JULY 2007 VOL. 27, NO. 4 THE SHORT PET IN PEDIATRICS Farris K. Short peritoneal equilibration test: impact of preceding dwell time. Adv Perit Dial 2003; 19: DuBois D, DuBois EF. A formula to estimate the approximate surface area if height and weight be known. Arch Intern Med 1916; 17: Morgenstern BZ. Equilibration testing: close, but not quite right [Editorial comment]. Pediatr Nephrol 1993; 7: Centers for Medicare & Medicaid Services annual report: End Stage Renal Disease Clinical Performance Measures Project. Am J Kidney Dis 2006; 48(Suppl 2):S