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1 Original Article Peritoneal Equilibration Test (PET) Analysis among Filipino Children on Chronic Peritoneal Dialysis at the National Kidney and Transplant Institute: A Cross-Sectional Study Elmer Kent A. Lopez, MD, Malou Saga-Valdez, MD, Zenaida L. Antonio, MD, Ofelia R. De Leon, MD, Ma. Angeles G. Marbella, MD, Violeta M. Valderrama, MD, Ma. Lorna Lourdes L. Simangan, MD ABSTRACT Background: Peritoneal Equilibration Test (PET) is a simple means of characterizing solute transport rates across the peritoneum. It may supply useful information on peritoneal solute transfer characteristics in children on peritoneal dialysis (PD) and facilitate individualized PD prescription. Objective: To determine the peritoneal membrane characteristics of Filipino children by performing PET to children on chronic peritoneal dialysis, thereby classifying them into low, low- average, high-average and high transport types. Methods: The study was conducted at the National Kidney and Transplant Institute, Department of Pediatric Nephrology Out-patient Clinic using purposive convenient sampling. A PET was done to each patient. Data analysis was carried out using frequency, percentage distribution, mean and standard deviation in analyzing the demographic characteristics. One-Way Analysis of Variance and Pearson Chi-Square Test/Fisher-Exact Test were used in determining association between PET and possible factors affecting its result at 0.05 level of significance. Results: A total of 30 pediatric patients on chronic peritoneal dialysis were enrolled. Majority of subjects were predominantly adolescents, with a mean age of years old. There were 60% males and 40% females. Chronic glomerulonephritis was the leading cause of ESRD in 83.3%. Seventy seven percent of the population had normal BMI for age and sex percentile, followed by 20% underweight subjects and a case of overweight (3%). PET results revealed 53.3% as low average transporters, 30% as low transporters while 16.7% as high average transporters. Conclusion: Filipino children on chronic peritoneal dialysis in a specialty center were predominantly classified as low average transporters, followed by low transport type category. There was no significant association between PET type and factors: age, sex, cause of ESRD, weight, height, body surface area (BSA), body mass index (BMI) and duration of dialysis. Key words: dialysis adequacy, pediatric, peritoneal dialysis, peritoneal equilibration test (PET), peritoneal function test Received: 7 August Accepted: 29 September Corresponding author: Elmer Kent A. Lopez, MD Department of Pediatric Nephrology, National Kidney Institute East Avenue, Diliman, Quezon City 1100, Philippines Tel. No.: (63) , local 2172 Fax No.: (63) / doktorkent@yahoo.com; nktipedianephro@gmail.com Copyright 2017 PJN is an OPEN-ACCESS publication, wherein all published articles/materials are open to be used to expand the body of knowledge in the field of Medicine - Nephrology, for non-commercial purposes, provided the article/s used are properly cited and recognized according to International Creative Commons License Attribution-Noncommercial-Share Alike 4.0 [CC BY-NC-SA 4.0]. 6 Vol. 25 No. 1 October 2017

2 INTRODUCTION The high and increasing incidence of end-stage renal disease (ESRD) is consuming a major portion of health care resources for both pediatric and adult populations. While the incidence rates for pediatric ESRD have remained relatively constant at 14 million children under the age of 19 years, many adults with ESRD suffer from a kidney disease that began as chronic kidney disease (CKD) during childhood. 1 In the Philippines, there were 97 new cases of CKD recorded in 2014 which constitutes 6.4% of the renal admissions and admission referrals according to unpublished Pediatric Renal Census of the Pediatric Nephrology Society of the Philippines (PNSP) in which 52% of them were initiated on peritoneal dialysis (Valderrama V, 2014, unpublished data). Peritoneal dialysis (PD) represents a well-established dialysis modality for pediatric patients. It is currently the dialysis treatment modality most commonly prescribed for children and adolescents that offers several advantages over hemodialysis (HD). 1 However, a significant number of patients drop out of peritoneal dialysis due to inadequate dialysis. Experience shows that an appropriate regimen on one patient may not be sufficient for another. 2 A Peritoneal Equilibration Test (PET) evaluation conducted soon after the initiation of dialysis to determine the transport capacity of a patient s peritoneal membrane is an important factor in determining the optimal dialysis prescription. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) clinical practice guideline for peritoneal dialysis adequacy recommends peritoneal membrane transport testing when clinically indicated. 3 The PET is a semi-quantitative assessment of peritoneal membrane transport function in patients on peritoneal dialysis. 4 The standardized PET developed by Zbylut Twardowski defines the peritoneal membrane s clearance and ultrafiltration rates by measuring dialysate to plasma ratios of creatinine and glucose under special conditions. Once membrane permeability is identified, clinicians can more accurately select a PD regimen to optimize dialysis based upon other parameters such as patient weight, food consumption and urea generation rates. 3 Presently, PET in children is not being widely utilized in our country. Its determination among pediatric patients is of great importance in optimizing peritoneal treatment prescription to achieve significant adequacy in dialysis treatment. A preliminary study on the evaluation of PET among Filipino children on chronic peritoneal dialysis using Baxter system in our institute was done in 2011 but the study population then was small. Hence, this study was conducted as a follow up study on the evaluation of PET using the Fresenius system. OBJECTIVES The main objective of the study was to determine the peritoneal membrane characteristics of Filipino children on chronic peritoneal dialysis (CPD) at NKTI by performing PET. Specifically, it aimed to determine the demographic profile and baseline characteristics of children on CPD and classify patients as to peritoneal membrane transport type. Lastly, to determine the association of PET type as to age, sex, cause of ESRD, weight, height, body surface area (BSA), body mass index (BMI) and duration of dialysis. METHODS This was a follow up baseline study on peritoneal equilibration test on pediatric patients on chronic peritoneal dialysis in tertiary subspecialty center. The sample size was determined based on the previous preliminary study of 7 subjects of the same study design. A purposive convenient sampling wherein 30 available children aged 18 years old and below, maintained on chronic peritoneal dialysis for at least 1 month at NKTI were enrolled in this cross-sectional prospective study. Excluded were patients who had history of peritonitis within a month prior to study, dehydrated or fluid overloaded and those with PD Vol. 25 No. October 2017 ww.pjnonline.com 7

3 catheter malfunctioning. It was performed at the Department of Pediatric Nephrology Out-patient Department (NKTI-OPD). All subjects were recruited in both pay and service clinics. Personal Information Sheet (PIS), as well as informed consent or assent was obtained before participation as approved by the Institutional Review Board (IRB). Anonymity of the subjects was maintained by giving unique numbers for identification. Confidentiality of the results and information gathered from the study was also observed. A Peritoneal Equilibration Test of Fresenius system protocol was done in each patient after clinical consultation. Patients were required to have a complete drainage after 8- to 12-hour overnight drain prior to the study. A fresh 2.3% glucose peritoneal dialysis solution was infused with the volume of 1100ml/m 2 BSA. A 10ml-dialysate sample was sent to laboratory for creatinine and glucose determination at 0-hour (PET 1), 2-hour (PET 2) and 4-hour (PET 3) dwell time. At 2-hour dwell time, blood sample was also extracted for serum creatinine and glucose. The remaining volume was drained, weighed and recorded. For the correction factor, creatinine and glucose were determined from a new 2.3% dialysate. PET was computed using ratio of dialysate creatinine and plasma creatinine (D/P crea) and was interpreted accordingly. For data analysis, descriptive analysis was carried out by using mean and standard deviation for continuous variables while frequency and percentage distribution for categorical variables. One-Way Analysis of Variance (ANOVA) was utilized for inferential analysis of continuous variables while Pearson Chi-Square Test or Fischer Exact Test for categorical variables at 0.05 level of significance. RESULTS The study population included 30 pediatric patients on chronic peritoneal dialysis. All of them were newly diagnosed pediatric ESRD patients from January 2013 to December 2014 maintained on CAPD at 4 exchanges per day regimen. The summary of the demographic characteristics of the study participants is shown in Tables 1 and 2. Table 1. Characteristics of study participants (n=30) Demographic characteristics Minimum Maximum Mean Std Deviation Age (years) Duration of PD (months) BMI (kg/m 2) PET (D/P crea) Table 2. Demographic characteristics of study participants (n=30) Demographic characteristic Frequency % Sex Male Female Native renal disease Chronic glomerulonephritis IgM nephropathy Membranoproliferative GN Focal segmental GN IgA nephropathy Dysplastic kidneys Nutritional status Normal Underweight Overweight Type of transporter Low Average High Majority of subjects were predominantly adolescents, with a mean age of years old. Average duration of peritoneal dialysis was months. There were 60% males and 40% females. Chronic glomerulonephritis was the leading cause of ESRD in 83.3%. Seventy seven percent of the population had normal BMI for age and sex percentile, followed by 20% underweight subjects and a case of overweight (3%). 8 Vol. 25 No. 1 October 2017

4 As shown in Figure 1, PET (D/P crea) results revealed 53.3% as low average transporters, 30% as low transporters while 16.7% as high average transporters. No subjects were classified as high transporters. 16.7% Figure 1. Distribution of subjects as to type of transporter. Pearson Chi-Square Test or Fischer Exact Test revealed that sex, native renal disease and nutritional status showed no proven association with the type of transporters (Table 3). One-way ANOVA revealed that there was no statistical significant correlation between PET (D/P crea) and age, duration of peritoneal dialysis and body mass index (Table 4). DISCUSSION 53.3% 30% Low Low Average High Average Peritoneal equilibration test (PET) is an easy, inexpensive and reliable test to assess peritoneal transport type and provide information about peritoneal clearance of solutes and ultrafiltration. Peritoneal transport type classification is recognized not only as an aid for prescription, but also as a prognostic index. 5 Results from the PET classify patients into 4 basic groups, namely low, low average, high average and high transporters. 6 Low transporters have 4-hour D/P crea <0.49 and high D/D0 glucose and a high net ultrafiltration volume. Low average transporters have a D/P crea at 4 hours between 0.50 and They would be expected to have high average D/D0 glucose and high average net ultrafiltration values. High Table 3. Association of categorical variables to type of transporter Type of transporter Low Average High Demographic characteristic Count Col% Count Col% Count Col% p-value + Sex 0.41 Male Female Native renal disease 0.97 Chronic glomerulonephritis IgM nephropathy Membrano proliferative GN Focal segmental GN IgA nephropathy Dysplastic kidneys Nutritional status Normal Underweight Overweight Total p- value < 0.05 statistically significant association Table 4. Association of continuous variables to type of transporter Demographic characteristic (profile) Age (years) Duration of PD (months) BMI (kg/m 2 ) n Mean Std Min Max p deviation value+ Low Average High Total Low Average High Total Low Average High Total p- value < 0.05 statistically significant association10 Vol. 25 No. 1 October

5 average transporters have a 4-hour D/P crea between 0.65 and 0.81 and would also be expected to have low average values for average net filtration. High transporters have a D/P creatinine at 4 hours >0.82 and would be expected to have low D/D0 glucose and low net filtration. In this study, great majority of pediatric patients on chronic peritoneal dialysis were classified as low average transporters (53.3%). They have good net ultrafiltration and adequate solute clearance which best require standard CAPD dose. Low transport type ranked second (30%). This transport type has inadequate solute clearance but with excellent net ultrafitration which requires high dose, longer dwell CAPD or hemodialysis. The remaining 16.7% were high average transporters which have both adequate solute clearance and net ultrafiltration which best prefer any regimen. No patients fit under high transport type category which have excellent solute clearance and but with poor net ultrafiltration that require automated peritoneal dialysis (APD) regimen. These findings are consistent with the unpublished preliminary results of similar study done at NKTI which revealed four out of seven Filipino children were classified as low average transporters (Saga- Valdez, 2011,unpublished data). However, in the study of Liu et al., among children between 2-14 years old, PET showed 70% of CAPD Chinese children fit into high and high average transport categories. 7 The same trending was also reported in the study of Aksu et al., in 21 Turkish children on CAPD. 8 Extreme difference of age groups between both studies showed contrasting results of PET. Although this is speculative, age group could possibly affect the transport type in children, favoring low and low average transport type to older age groups. This may mean the older and the bigger were the subjects, the lower would be the PET value. This may be the reason why Filipino children in this study tend to be low and low average transporters since our study subjects were predominantly adolescents (84%) who were bigger in size and weight. If ever we had greater number of younger patients in our study, then probably there were some subjects fit into high transport type category. In a study by Mendley et al., found out American children age 2 years old and below transport glucose and creatinine more rapidly than do children 3 to 14 years old and adults. Children 3 to 14 years old transport glucose more rapidly than do adults. 9 As also cited in the study of Schaefer et al., the transfer rates of most solutes were correlated with each other but individual variation of peritoneal permeability for different solutes was high. The permeability of all solutes tended to be inversely correlated with body size. 10 Exact correlation was not exhibited in our study since study subjects were mostly adolescents and no patients below 6 years old were included. Similar with adults, Filipino children in our PET study had the same transport type category comparable to the study by Uncanin et al., in which 63.3% of Bosnian adults who were low average transporters. 5 Adults and adolescents probably have nearly similar physiologic and anatomic peritoneal functions. More than 50% of our patients in this study were young adults who may be already attained the same transport type capacity and function with that of adult peritoneal system. However, factors possibly affecting PET such as age, sex, cause of ESRD, weight, height, BSA, BMI and duration of peritoneal dialysis revealed no significant correlation to PET in this study (P-value > 0.05). Nonetheless, this finding cannot be generalized due to the sample size factor and that the study population was not normally distributed. In the study of Avellan-Boza et al., there were also no significant differences between age, gender, diabetes mellitus, serum albumin, C reactive protein and the type of peritoneal transport, even when previous studies have revealed a higher proportion of men, diabetic patients and low serum albumin 10 Vol. 25 No. 1 October 2017

6 concentration in the high transporter group in adult Costa Rican cohorts. 11 However, in a PET study in Australia and New Zealand with 3,188 adult patients, high transporter PET was associated with increased age and ethnicity but not associated with gender, diabetes and other co-morbid conditions, smoking, previous hemodialysis therapy or transplantation, or residual renal function. 12 A similar association between increasing age and high transporter status at dialysis initiation was noted in a second smaller study from Spain. 13 There were limited published literatures about PET used in the evaluation of PD adequacy especially among Asian children. Hence, the results of this study may be used as pioneer baseline data for PET among Filipino children on chronic peritoneal dialysis. However, further studies are encouraged to address the limitations to yield more valid and meaningful conclusion. CONCLUSION The author concludes that Filipino children on CPD in a specialty center were predominantly classified as low average transporters, followed by low transport type category. They best require standard CAPD regimen and high dose, long dwell time CAPD, respectively. Furthermore, no significant association was confirmed between PET (D/P crea) and possible factors affecting its result such as age, sex, native renal disease, weight, height, BSA, BMI and duration of peritoneal dialysis. Recommendations Larger sample population is recommended to assess correlation of PET across possible factors affecting its result such as age, sex, cause of ESRD, weight, height, BSA, BMI and duration of dialysis. Random sampling method of selecting subjects is also highly recommended. Multicenter studies should also be conducted to achieve a valid conclusive finding of PET among Filipino children on chronic peritoneal dialysis. Funding/Disclosure The Department of Pediatric Nephrology of NKTI solely funded this research project. There were no outside sources of funding like pharmaceutical company taken in the completion of this study. About the Paper This research paper placed 2nd (Oral Presentation) in the Annual Completed Research Contest during 36th PSN Annual Convention, last April 21, 2016 at EDSA Shangri-La Hotel, Mandaluyong City, Manila. It placed 2 nd (Oral Presentation) in the Research Contest, Prospective Category, Annual Research Forum 2015, Dec 9, 2015, Dr. Enrique T. Ona Auditorium, NKTI, East Ave, Quezon City. It was presented orally during the Research Forum of the 21st PNSP Annual Convention, Nov 20, 2015, Crown Plaza Hotel, Ortigas Ave, Pasay City. Author Details National Kidney and Transplant Institute REFERENCES 1. Avner ED, Harmon WE, Niaudet P, Yoshikawa N (eds). Pediatric Nephrology, 6 th edition. Berlin: Springer- Verlag, Peritoneal dialysis policies, procedure and guidelines, Da Vita Inc. Policy: internalmedicine/files/2013/10/07-adequacy- Peritoneal-Dialysis.pdf. 3. Peritoneal Dialysis Adequacy Work Group. Clinical practice guidelines for peritoneal dialysis adequacy. Am J Kidney Dis. 2006;48 Supp 1:S PMID: DOI: /j.ajkd Misra M, Khanna R. The clinical interpretation of peritoneal equilibration test. Semin Dial. 2014;27(6): PMID: DOI: /sdi Uncanin S, Rasić S, Rebić B, et al. The importance of using peritoneal equilibration test for the peritoneal transport type characterization in ambulatory periotenal Vol. 25 No. 1 October

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