WM Lai, MC Chiu, KC Tse, SC Lau, PC Tong

Abstract

We report the 6 ½ years experience of automated peritoneal dialysis (APD) in 32 Chinese children who were put on the APD programme in the Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital since November 1996. There were 15 boys and 17 girls and the mean age of start of APD was 11.2±5.8 years (range 0.1-21.5 years). The mean duration of APD was 27.7±22.3 months (range 3-79 months). The primary diagnosis were glomerulonephropathies (40.6%), hypoplastic/dysplastic kidneys (31.3%), pyelonephritis (9.4%), and other renal diseases (18.8%). Peritoneal equilibration test showed that 14 patients (48.3%) were high transporter, 10 patients (34.5%) were high average transporter and 4 patients (13.8%) were low average transporter. Seven patients (21.8%) were on nightly intermittent peritoneal dialysis. Seventeen patients (53.1%) on continuous cyclic peritoneal dialysis (CCPD), 4 patients (12.5%) on high dose CCPD, and 3 patients (9%) on tidal peritoneal dialysis. The incidence of peritonitis rate was low with 1 infection every 80.5 patient months or annualised peritonitis rate 0.149. Causative organisms included gram positive organisms (45.5%), gram negative organisms (27.2%), atypical mycobacterium (9%), and culture negative (18.2%). The incidence of exit site infection was 1 episode per 23.5 patient months. The mean weekly Kt/V urea was 2.46±0.58 and mean combined weekly creatinine clearance was 59.3±19.5 litre/1.73 m². Eighteen patients (56.2%) remained on APD. Ten patients (31.3%) were successfully transplanted with functioning graft. One patient (3.1%) was on chronic HD and there were 3 deaths. We concluded that APD is a good dialysis modality for paediatric end stage renal failure patients and there was a low incidence of peritonitis while achieving adequate dialysis in the majority of patients.

Introduction

Chronic peritoneal dialysis (CPD) has emerged as the preferred paediatric dialysis modality due to its superior flexibility and compatibility with children's lifestyle habits. In North America, paediatric dialysis programs favour the use of peritoneal dialysis (PD) by 2:1 over haemodialysis (HD).¹ After its first use in a child in 1978 in Toronto, continuous ambulatory peritoneal dialysis (CAPD) has been the most commonly prescribed dialysis modalities for children with end stage renal disease (ESRD). However, in the last decade, there has been a rapid growth of automated peritoneal dialysis (APD) where a cycler machine is used for infusion and drainage of peritoneal solution. The significant advantages of APD for lifestyle and social rehabilitation as well as allowance for delivery of higher dose of dialysis than CAPD made it the preferred form of CPD for paediatric dialysis. Data from different national registries of CPD showed that the proportion of APD ranged from 62% to 91%.^2-6 In this study, we reviewed our 6 ½ years' experience of the epidemiology, prescription, and outcomes of children on APD.

Patients and Methods

We reviewed our center's experience of 32 patients (15 boys, 17 girls) with ESRD started on APD from November 1996 to July 2003 at the Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital. The APD program for paediatric ESRD patients started in November 1996 with the support from the Children's Kidney Trust Fund.

Peritoneal equilibration test (PET) was done after initiation of dialysis and once every year to characterise the solute transport rates cross the peritoneum. It was performed with a PD 2.5% dialysate with volume scaled to BSA of 1,100 ml/m². The patient's solute dialysate-to-plasma ratios can then compare with published value to characterise the patient's peritoneal transport capacity into high, high-average, low-average, and low transporter on which to guide the PD prescription.^7-9

APD was carried out at night by the cycler machine with the child in bed either without daytime dwell (nightly intermittent peritoneal dialysis, NIPD), or with daytime dwell (continuous cyclic peritoneal dialysis, CCPD), or with one or two exchanges before the night session (high dose continuous peritoneal dialysis, high dose CCPD), or with only partial drainage of the overnight cycles (tidal peritoneal dialysis, TPD) (Figure 1).¹⁰ The regimens included 8-12 hours of continuous cycling of PD with fill volume of 1,000-1,400 ml/m² per cycle using PD dialysate, 1.5%, 2.5%, and 4.25% in various combination depending on the ultrafiltration requirement of the patient. The PD prescription was individualised and was based on the peritoneal transport membrane characteristics, and residual renal function (RRF).

Figure 1 Different modalities of automated peritoneal dialysis: CCPD, with nocturnal exchanges and daily long dwell; High dose CCPD where one or two daily exchanges are performed after a nocturnal session; NIPD, with complete drainage every cycle during the night and a daytime dry cavity. Tidal modality is the same as NIPD but with incomplete drainage (50%) every cycle.

The dialysis adequacy was monitored in terms of small solute clearance as a total (residual renal+PD) weekly Kt/V urea and a total weekly creatinine clearance. 24 hours collections of urine and dialysate fluid were performed 2-4 times per year.

Peritonitis is defined as cloudy peritoneal effluent, with dialysate white blood cell count greater than 100 cells/uL, with >50% neutrophil. Fever, abdominal pain, or positive culture were not a requirement for diagnosis.¹¹

Results

The mean age at start of APD was 11.2±5.8 years (range 0.1-21.5 years) (Figure 2) and the mean duration on APD was 27.7±22.3 months (range 3-79 months). The most common primary diseases for ESRD were chronic glomerulonephritis (40.6%), followed by those with renal hypodysplasia/dysplasia (31.3%), reflux nephropathy (9.4%), and other renal disorders (18.8%) (Table 1).

Figure 2 Age at start of APD.

PD Prescription

Seven patients (21.8%) were on NIPD, 17 patients (53.1%) on CCPD, 4 patients (12.5%) on high dose CCPD and 3 patients (9.4%) on tidal PD (Figure 3).

Figure 3 Automated peritoneal dialysis regimens. Nightly intermittent peritoneal dialysis (NIPD); Continuous cyclic peritoneal dialysis (CCPD); High dose CCPD; Tidal peritoneal dialysis (TPD).

Peritonitis and Exit Site Infection (ESI)

During a total of 885 APD patient months, there were a total of 11 episodes of peritonitis in 8 patients. About 25% of all APD patients experienced one or more episode of peritonitis. The incidence of peritonitis was 1 episode every 80.5 patient months and the annualised peritonitis rate was 0.149. Gram-positive organisms were responsible for the majority of cases (45.5%), followed by gram-negative organisms (27.2%), culture negative (18.2%), and atypical mycobacteria (9%) (Figure 4). Two patients were switched to chronic hemodialysis because of the peritonitis. The incidence of exit site infection was 1 episode every 23.5 patient months. Staphylococcus aureus (42.3%) and pseudomonas aeruginosa (38.4%) accounted for the majority of cases of ESI.

Figure 4 Causative organism of peritonitis.

PD Adequacy

Twenty-nine patients had PET and showed that 14 patients were high transporter (48.3%), 10 patients were high average transporter (34.5%), 4 patients were low average transporters (13.8%) , and 1 patient was low transporter (3.4%) (Figure 5). Mean Kt/V urea was 2.46±0.58 (Figure 6). Mean weekly creatinine clearance was 59.3±19.5 Litre/week/1.73 m² (Figure 7).

Figure 5 Peritoneal equilibration test.

Figure 6 Kt/v urea of patients on APD.

Figure 7 Weekly combined creatinine clearance (L/week/1.73 m2) of patients on APD.

Outcome

Eighteen patients (56.2%) remained on APD, 10 patients (31.3%) were successfully transplanted with functioning graft, and 1 patient (3.1%) was on chronic HD. There were 3 deaths (9.4%): one mentally retarded patient died of cardiovascular complication, one patient with Wegener's granulomatosis died of relapse of the disease and aspergillosis, and one infant with congenital nephrotic syndrome died of sepsis.

Discussion

There is a worldwide preference of APD as the dialysis modality of choice in children with end stage renal failure. It is physically much simpler, requiring setting up a cycler machine once at night with uninterrupted daytime activities. It allows the children to attend school full-time, and reduce the impact of PD treatment on the way of life of the patients and their families. The freedom from dialysis during daytime gives the children a sense of feeling more "normal" than CAPD or HD.¹² It can deliver higher dialysis dose than CAPD and because of the wide range of APD prescription regimens available, it can provide a dialytic schedule which is tailored to the needs of the individual paediatric patients.

In view of the significant advantages of APD for lifestyle and social rehabilitation, APD has become the preferred mode of CPD for our paediatric patients and has completely replaced CAPD in the past seven years or so of peritoneal dialysis delivery.

There are different treatment options of APD and the APD prescription should be individualised basing on the body surface area, the peritoneal membrane solute transport characteristic from the PET results, and residual renal function.¹ NIPD permits the patient to attend to all his daily activities with empty abdomen, and hence a better quality of life. This modality is suitable for patients with high and high average transporter with adequate residual renal function.¹³ Seven patients (21.8%) were on NIPD. All of them were high or high average transporters. CCPD with daytime dwell is suitable for low average or high average transporters and when the residual renal function gradually decreases.¹³ Seventeen of our patients (53.1%) were on CCPD. High dose CCPD with extra daytime exchanges apart from the night time exchanges are required when the residual renal function is minimal or absent. In 4 of our patients (12.5 %), high dose CCPD were required to optimise the dialysis adequacy. TPD starts with an initial fill volume and is followed by a partial drainage of PD fluid, which provides higher clearances of small molecules and higher ultrafiltraion.¹³ Three of our patients (9.4%) were on TPD, of whom 2 had problem of fluid retention while on CCPD and 1 had fluid retention and inadequate dialysis adequacy.

The PET was developed by Twardowski et al⁷ to characterise the peritoneal membrane transport rates (high, high average, low average, low) which have a significant influence on the dialysis clearance and on the PD prescription. In general, high and high average transporters are more suitable to use APD than CAPD because of the short cycles used in APD. Since most of our patients (82.8%) were high or high average transporters, therefore they are more likely to reach goals of adequacy in treatment and good fluid control with APD.

Peritoneal dialysis related infections, especially peritonitis, are the major complications leading to adverse consequences in children including hospitalisation, catheter replacement, damage to the peritoneal membrane function and technique failure. It is essential to prevent peritonitis in children on peritoneal dialysis in order to preserve the peritoneal membrane function and decrease the dropout and technique failure. In CAPD, with the advent of connectology device, the peritonitis rate using double bag system still remained at 1 episode per 24 to 34 patients months.¹⁴ There were conflicting earlier reports on whether CAPD or APD had lower peritonitis rate. However, recent adult studies have shown a trend toward lower peritonitis rates in APD compared to CAPD.^15-16 The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) in comparing the incidence and outcome of CAPD and APD in children, showed that the incidence and time to first peritonitis episode were significantly better in APD children.¹⁷ In the United States, the overall peritonitis rate from the reports of the NAPRTCS range from 1 episode per 13.2 patient months in earlier reports^3,18 to recent report of 1 episode per 14.7 patient months.² In Japanese children, the peritonitis rate is lower at 1 episodes per 30 patient months.⁵ In our APD children, the rate of peritonitis is 1 episode per 80.5 patient months which is very low as compared with other reports. Since the mean waiting time for local cadaveric renal transplantation is long (4.4 years as compared to that of 1.4 years in USA), the low peritonitis rate is particularly important for our ESRD children as it can preserve the peritoneal membrane function and the children can be maintained on peritoneal dialysis for a longer period of time.

It is recommended that most dialysis should be delivered to the patient within the constraints of social and clinical circumstances, quality of life, and cost. The adequacy of PD should include the patient's clinical condition with attention to the presence of uremic symptoms, nutritional state, growth, and school or vocational performance.¹ In addition, measurement of PD dose in terms of small solute clearance by weekly Kt/V urea or total weekly creatinine clearance which have been associated with mortality and morbidity in adult studies,^19-20 should be monitored regularly during PD. Current recommendations form the National Kidney Foundation - Dialysis Outcome Quality Initiative (NKF-DOQI) for the adequacy of APD are a Kt/v urea >= 2.1 per week and a total creatinine clearance Ccr >= 63 per week per 1.73 m².²¹ However, it is still controversial whether the DOQI targets can be achieved by dialysis in children on APD. In a report from by Voort et al, only 45% achieved a Kt/V urea of >= 2.1 and only 10% achieved a Ccr >= 63 L/wk per 1.73 m².²² The mean weekly Kt/V urea of our patients was 2.46±0.58 which was above the DOQI recommendation of 2.1. The mean total creatinine clearance Ccr of our patients was 59.3±19.5 L/week/1.73 m² which was slightly below the DOQI recommendation of 63 L/week/1.73 m². Majority of our APD patients achieve the current DOQI clearance targets, at least for Kt/V urea.

Conclusions

In conclusion, APD is the preferred mode of peritoneal dialysis modality in the management of paediatric patients with ESRD. This retrospective study reveals that there is a very low peritonitis rate and the majority of our APD patients can achieve adequate dialysis. Although renal transplantation remains the treatment of choice for paediatric patients with ESRD, APD can be a safe and effective alternative in cases where renal transplantation is not available.

References

1. Warady BA, Alexander SR, Watkins S, Kohaut E, Harmon WE. Optimal care of the pediatric end-stage renal disease patient on dialysis. Am J Kidney Dis 1999;33:567-83.

2. Neu AM, Ho PL, McDonald RA, Warady BA. Chronic dialysis in children and adolescents. The 2001 NAPRTCS Annual Report. Pediatr Nephrol 2002;17:656-63.

3. Lerner GR, Warady BA, Sullivan EK, Alexander SR. Chronic dialysis in children and adolescents. The 1996 annual report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Nephrol 1999;13:404-17.

4. Verrina E, Perfumo F, Gusmano R. Automated peritoneal dialysis prescription and results in children. Contrib Nephrol 1999;129:123-33.

5. Honda M. The 1997 Report of the Japanese National Registry data on pediatric peritoneal dialysis patients. Perit Dial Int 1999;19 Suppl 2:S473-8.

6. Verrina E, Perfumo F, Calevo MG, et al. The Italian Pediatric Chronic Peritoneal Dialysis Registry. Perit Dial Int 1999;19 Suppl 2:S479-83.

7. Twardoswki ZJ, Nolph KD, Khanna R, et al. Peritoneal equilibration test. Perit Dial Bull 1987;7:378-83.

8. Warady BA, Alexander SR, Hossli S, et al. Peritoneal membrane transport function in children receiving long-term dialysis. J Am Soc Nephrol 1996;7:2385-91.

9. Warady BA, Alexander S, Hossli S, Vonesh E, Geary D, Kohaut E. The relationship between intraperitoneal volume and solute transport in pediatric patients. Pediatric Peritoneal Dialysis Study Consortium. J Am Soc Nephrol 1995;5:1935-9.

10. Fischbach M, Terzic J, Bergere V, Gaugler C, Provot E. The optimal approach to peritoneal dialysis prescription in children. Perit Dial Int 1999;19 Suppl 2:S462-6.

11. Warady BA, Schaefer F, Holloway M, et al. Consensus guidelines for the treatment of peritonitis in pediatric patients receiving peritoneal dialysis. Perit Dial Int 2000;20:610-24.

12. Blake PG. Advantages and disadvantages of automated peritoneal dialysis compared to continuous ambulatory peritoneal dialysis. Perit Dial Int 1999;19 Suppl 2:S121-4.

13. Dell'Aquila R, Rodighiero MP, Bordoni V, D'Intini V, Ronco C. APD prescription: achieving the adequacy goals. Semin Dial 2002;15:397-402.

14. Daly CD, Campbell MK, MacLeod AM, et al. Do the Y-set and double-bag systems reduce the incidence of CAPD peritonitis? A systematic review of randomized controlled trials. Nephrol Dial Transplant 2001;16:341-7.

15. Bro S, Bjorner JB, Tofte-Jensen P, et al. A prospective, randomized multicenter study comparing APD and CAPD treatment. Perit Dial Int 1999;19:526-33.

16. Fernandez Rodriguez AM, Vega Diaz N, Palop Cubillo L, et al. Adequacy of dialysis in automated peritoneal dialysis: a clinical experience. Perit Dial Int 1997;17:442-8.

17. Fine RN, Ho M, North American Pediatric Renal Transplant Cooperative Study. The role of APD in the management of pediatric patients: a report of the North American Pediatric Renal Transplant Cooperative Study. Semin Dial 2002;15:427-9.

18. Furth SL, Donaldson LA, Sullivan EK, Watkins SL, North American Pediatric Renal Transplant Cooperative Study. Peritoneal dialysis catheter infections and peritonitis in children: a report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Nephrol 2000;15(3-4):179-82.

19. Adequacy of dialysis and nutrition in continuous peritoneal dialysis: association with clinical outcomes. Canada-USA (CANUSA) Peritoneal Dialysis Study Group. J Am Soc Nephrol 1996;7:198-207.

20. Davies SJ, Phillips L, Griffiths AM, Naish PF, Russell GI. Analysis of the effects of increasing delivered dialysis treatment to malnourished peritoneal dialysis patients. Kidney Int 2000;57:1743-54.

21. National kidney foundation K/DOQI clinical practice guidelines for peritoneal dialysis adequacy. Am J Kidney Dis 2001;37(1 Suppl 1):S65-136.

22. van der Voort JH, Harvey EA, Braj B, Geary DF. Can the DOQI guidelines be met by peritoneal dialysis alone in pediatric patients? Dialysis Outcomes Quality Initiative. Pediatr Nephrol 2000;14(8-9):717-9.