Nutritional effects of increasing dialysis dose by adding an icodextrin daytime dwell to Nocturnal Intermittent Peritoneal Dialysis (NIPD) in children

Koen J. M. Van Hoeck1,2,, Esther Rusthoven2, Linda Vermeylen1, Annemie Vandesompel1, Bart Marescau3, Marc Lilien2 and Cornelis H. Schroder2

1 Department of Pediatric Nephrology, University Hospital Antwerp, Belgium, 2 Department of Pediatric Nephrology, University Medical Centre, Utrecht, The Netherlands and 3 Department of Neurochemistry University Antwerp (UIA), Belgium



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
 References
 
Background. To assess the need to adapt dietary prescriptions, we studied potential effects of increasing the dialysis dose by adding a daytime icodextrin dwell, in children on Nocturnal Intermittent Peritoneal Dialysis (NIPD), on peritoneal amino acids (AA) and albumin loss, AA, albumin, cholesterol and fibrinogen plasma levels and nutritional intake.

Methods. A cross-over study in eight children (age 2–12 years) on NIPD at baseline (week 1). Intervention: to increase dialysis dose we added a daytime dwell with 1100 ml/m2 icodextrin solution for a week (week 2). Main outcome measures: peritoneal albumin loss (quantified by nephelometry) and AA loss (quantified by liquid chromatography mass spectrometry) in the last 72 h dialysate collections of weeks 1 and 2. On days 7 and 14, morning blood sample was taken for urea, creatinine, plasma AA levels, serum albumin, cholesterol and fibrinogen determination. Nutritional intake diaries were kept throughout the study period.

Results. Weekly dialysis creatinine clearance increased from 35 to 65 l/1.73 m2 (P<0.0001) and Kt/V from 1.99 to 2.54 (P<0.01). Peritoneal albumin loss did not change significantly (2.4±0.4 to 2.4±0.3 g/m2/24 h) nor did serum albumin (3.25±0.52 to 3.21±0.25 g/dl), cholesterol (216±73 to 240±61 mg/dl) and fibrinogen (385±40 to 436±64 mg/dl). There was a significant increase in loss of essential (EAA) [1122±200 to 2104±417 mg/m2/week (P<0.0001)] and non-essential amino acids (NEAA) [6160±1341 to 10406±2899 mg/m2/week (P<0.001)]. Plasma AA levels did not change significantly except for a drop in histidine and glutamine. Dietary protein intake did not change from 43±12 to 41±8 g/m2/day, caloric intake from 73±21 to 70±24 kcal/kg/day.

Conclusions. Increasing dialysis dose by introducing a daytime icodextrin dwell during a week does not affect peritoneal albumin loss, serum albumin, cholesterol and fibrinogen levels nor dietary intake on a short term. There is a significant increase in EAA and NEAA loss without change in plasma levels. We suggest monitoring dietary intake when adding a daytime icodextrin dwell in children.

Keywords: amino acids; children; dialysis dose; icodextrin; peritoneal dialysis



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
 References
 
Polymer-based peritoneal dialysate solutions were designed to treat ultrafiltration failure in patients, especially when caused by high glucose absorption due to high transport peritoneal membranes [1]. The use of a single nighttime dwell with icodextrin solution offers equal ultrafiltration for patients treated with glucose 3.86% and is now widely used in adult patients [1]. Moreover, icodextrin has beneficial effects on the peritoneal membrane and long-term use of this solution could improve technique and patient survival [24].

Although the safety of short-term use of icodextrin in children has been documented, it has not been studied extensively in paediatric patients [5]. In children with inadequate ultrafiltration or dialysis on nighttime intermittent automated peritoneal dialysis (NIPD), adding a single daytime dwell of icodextrin is a tempting therapeutic option, offering the above-mentioned advantages to a daytime high glucose 3.86% exposure. However, extra loss of nutrients in the daytime dialysate, like albumin and essential amino acids (EAA), could be a side effect. Although this loss has never been properly documented with NIPD or continuous cycling peritoneal dialysis (CCPD), extra loss of protein and amino acids (AA) was suggested by studies in children treated with CAPD [6]. Moreover, a filled abdominal cavity during the day could lead to loss of appetite, further compromising nutritional status compared with NIPD.

To assess the need to adapt nutritional prescriptions when increasing dialysis dose we prospectively studied the effect of a 1-week extra icodextrin daytime dwell on Kt/V urea and creatinine clearance, peritoneal albumin and AA loss, nutritional intake and serum albumin, cholesterol and fibrinogen levels and plasma AA levels in eight children.



   Subjects and methods
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
 References
 
Eight children (six boys) aged 2–12 years treated with NIPD for >3 months were enrolled after parental informed consent was obtained. The study was performed at least 3 months after the last peritonitis episode. Patient's characteristics are shown in Table 1Go. During the first week, observation of the baseline therapy with the use of home recording of nutritional intake with 7-day diary, ultrafiltration results, blood pressure and body weight was carried out. NIPD was performed with the patient's personal regimen (Table 1Go). The last three nights of the observation week all spent dialysate was collected and frozen. The morning of day 7, a fasting blood sample for serum urea, creatinine, albumin, cholesterol, fibrinogen and AA analysis was drawn by the study nurse at the patient's home. The frozen dialysates were collected and shipped to the laboratory for storage at -20°C until analysis.


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Table 1.  Patient characteristics; baseline dialysis treatment and result of the PET test before inclusion

 
The night following the blood sampling, NIPD therapy was extended with a daytime dwell of icodextrin. The volume equalled the usual NIPD dwell volume and the dwell time equalled the NIPD empty abdomen (daytime) period. As none of the patients had clinical signs of overhydration, the danger of dehydration was explained and increased water intake was accepted provided body weight and blood pressure stayed within a tolerable range. The same procedure as in week 1 was performed. Dialysis regimen did not change in any patient during the 14-day study period except for the addition of a daytime dwell. A blood sample was taken the morning of day 14. The patients then returned to their usual PD regimen. Dialysate was analysed for volume, creatinine, after correction for glucose, and urea content with standard techniques. Dialysate albumin was measured with the nephelometric method. A calibration curve for albumin concentration measurements in icodextrin containing dialysate was established. Analysis for AA in glucose and icodextrin dialysate was performed after separation over a cation exchange column using lithium citrate buffers. For colorimetric detection the ninhydrin method was used (Biotronik LC 6001, amino acid analyser, Biotronik, Maintal, Germany). Normal plasma AA values were obtained from a group of 100 age-matched children. Serum measurement of creatinine, urea, albumin, cholesterol and fibrinogen were performed in the clinical laboratory with standard techniques.

A paired t-test was used to compare the differences where appropriate. A P-value <0.05 was considered significant.



   Results
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
 References
 
Introduction of a daytime dwell significantly increased the mean creatinine clearance from 35 to 65 l/1.73 m2/week (P<0.001) and the weekly Kt/V urea from 1.99 to 2.54 (P<0.01) (Figure 1Go). Mean ultrafiltration increased from 574 to 724 ml/m2/24 h, but this difference failed to reach significance (P-value 0.08). The patient's weight or average blood pressure did not change.



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Fig. 1.  Weekly Kt/V urea with NIPD therapy during week 1 and with NIPD plus 1100 ml/m2 BSA icodextrin daytime dwell during week 2 in eight children.

 
Mean peritoneal albumin loss per 24 h did not change significantly from 2382±432 to 2417±316 mg/m2 body surface area (BSA). Icodextrin daytime dwell accounted for 30–40% of 24 h albumin loss, but the nighttime loss decreased by a comparable amount. Average serum albumin level changed from 3.25±0.52 to 3.21±0.25 g/dl; cholesterol from 216±73 to 240±61 mg/dl and fibrinogen from 385±40 to 436±64 mg/dl. These changes were not significant.

AA loss in the dialysate was calculated from the 3-day collections and multiplied by 2.33 to extrapolate weekly loss. Average weekly AA loss in the dialysate increased by 70% from 6160±1341 with NIPD to 10 406±2829 mg/m2 BSA with NIPD and icodextrin dwell (P<0.001). Individual increase up to 14.4 g/week was observed. The daytime dwell contained 2910±1137 mg/m2 BSA/week. The loss observed in the nighttime dwell also increased by 17% the second week to 7495±1962 mg/m2 BSA (P<0.01).

The weekly loss of essential AA (threonine, valine, methionine, leucine, isoleucine, phenylalanine, histidine and lysine) was 78% higher when dialysis dose was increased: 1283±224 mg/m2 BSA to 2281±482 mg/m2 BSA (P<0.0001) (Figure 2Go). The daytime dwell was responsible for 68% of total increased loss. Nighttime loss of EAA also increased the second week with 325 mg/m2 BSA to 1608±342 mg/m2 BSA (P<0.01).



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Fig. 2.  Weekly loss of EAA in mg/m2 BSA with NIPD therapy (week 1) and NIPD plus 1100 ml/m2 daytime icodextrin dwell therapy (week 2) in eight children.

 
Non-essential amino acid (NEAA) loss increased by 67% from 4877±1172 to 8124±2419 mg/m2/week (P<0.001). A daytime loss of 2237±935 mg/m2 BSA of NEAA contributed to 67% of the total increase.

The increase in loss of EAA was significant in every individual. The individual increase of NEAA was not significant.

The average concentration of EAA (except methionine and phenylalanine) was below the 25th percentile for age-matched controls. The plasma AA concentrations were not decreased further after a 1-week dwell, except for histidine. The concentration of NEAA was in the normal range except for citrulline (was high, >p97) and tyrosine (was low, <p3). It decreased significantly for glutamine but stayed in the normal range (Table 2Go). Average daily dietary calorie intake did not change significantly from 73±21 cal/kg to 70±24 kcal/kg/day. Average dietary protein intake did not change significantly from 43±12 to 41±8 g/m2 BSA/day. A total average peritoneal AA loss of 10 g/m2/week or 1.5 g/m2/day means that on average 3.5% of daily intake is lost due to PD.


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Table 2.  Plasma AA levels in micromol/dl with NIPD therapy (week 1) and NIPD + a daytime icodextrin dwell therapy (week 2) in eight children

 



   Discussion
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
 References
 
In adults the use of icodextrin has been proven safe and successful. Most reports provide data on the extra ultrafiltration obtained, allergic reactions to icodextrin and on the beneficial effect of glucose free dialysate on the peritoneal membrane [1,710]. Reports of the detrimental effects of high glucose on childrens peritoneum are not available. Over a life time period, children with end-stage renal disease are destined to be on dialysis for several years to bridge the periods between kidney transplantation. The dialysis therapy should be aimed at providing adequate renal replacement and nutrition but also avoiding peritoneal damage. Therefore, in view of the beneficial effect of icodextrin on the peritoneal membrane of adults, it looks interesting to avoid glucose by immediately adding icodextrin to a NIPD scheme in case of ultrafiltration failure or low adequacy in children. As it has been suggested from reports of children treated with CAPD that daytime loss of nutrients can be detrimental, we chose to study the addition of a icodextrin daytime dwell to a regular NIPD regimen to increase dialysis dose and assess the need to adapt dietary prescription [6,11].

We demonstrate a significant increase of both creatinine clearance and Kt/V urea by adding a daytime dwell with icodextrin. This has been documented by others in adults and by our group in children [5,8,10]. It is however not surprising that an increase in dwell volume and dialysis time improves adequacy parameters. Ultrafiltration increased in all children but not significantly. Although UF might have added clearance further improving adequacy parameters it might also have decreased residual renal clearance (RRC) by dehydration. We did not document the effect of changes in UF on RRC in this study. In the three children with anuria (no RRC) we demonstrated a rise in dialysis dose comparable in amount to the rise in the five other children. We allowed increase of fluid intake to keep bodyweight in balance thus preventing dehydration leading to reduced residual urinary output. We observed no clinical indication that residual renal function was lost during week 2. This suggests that the rise in dialysis dose is clinically significant and not achieved at the expense of a decreased RRC.

Albumin loss is not increased with the use of an icodextrin daytime dwell to increase dialysis dose. The amounts of 2500 mg/m2/day are in the range reported earlier in adults on CAPD [12,13]. Although 40% of total loss can be recovered from the icodextrin dwell, the nighttime glucose dwell contains 40% less albumin than in the control week. This suggests that in NIPD the first nighttime dwell clears the peritoneal cavity from albumin passively leaking during daytime. Albumin transport would therefore be independent from both contact time and volume. This requires confirmation by further study. The mechanism of albumin loss has been described by Krediet and suggested as a restricted Einstein–Stokes-dependent diffusion [12]. In adults, albumin transport remained unaltered with icodextrin nighttime dwell compared with glucose 4.85% solutions [14]. The lack of increase of albumin loss is reflected in the stability of the serum albumin level.

Children treated with peritoneal dialysis suffer from disturbed serum lipid profiles including hypercholesterolaemia and fibrinogenaemia [15,16]. Hypercholesterolaemia and hyperfibrinogenaemia in CAPD can be related to (nephrotic range) albumin loss. A relationship of low serum albumin and high fibrinogen, a cardiovascular risk factor has been described in nephrotic range albumin loss and in CAPD patients [13,17]. Anticipating increased albumin loss with higher dialysis dose due to the use of icodextrin daytime dwell in children, we studied the relation of serum albumin and peritoneal albumin loss with serum cholesterol and fibrinogen levels. Serum fibrinogen was high in most patients and did not change after 1-week icodextrin dwell, as did serum albumin. This is in accordance with the results of a study in adults treated for 1–28 months with icodextrin in which serum fibrinogen and cholesterol remained high despite a change in fasting insulin levels [18]. High glucose load due to glucose containing dialysate may be another contributing factor to hypercholesterolaemia [15]. Few data are known on the nutritional effects of icodextrin per se. After 6 weeks of an overnight icodextrin dwell in adults, a reduction of total serum cholesterol was seen compared with high glucose dwells [18,19]. To study the effects of icodextrin per se on glucose and lipid metabolism rather than the effect of increasing dialysis dose on intake and loss of nutrients we should have included a control group of children, treated with glucose 3.86% as a daytime dwell. Because of the small number of patients available and the longer time needed to study this mechanism, the clinically more relevant set up of optimizing dialysis was chosen. Further study is needed to document (long-term) effects of icodextrin per se on serum lipid profiles and serum albumin levels in a larger group of children.

We describe a significant increase in EAA loss in every patient when dialysis dose is increased with a daytime icodextrin dwell. The NEAA loss increases to a lesser degree. This suggests that AAs from daytime food intake are washed out by the daytime dwell. Daily total AA loss increases up to 3.5% of total protein intake. As dietary intake of protein and calories did not change over the study period, attention should be given to AA status with long-term use of daytime dwells with icodextrin.

Plasma AA profile did not change significantly except for a drop in the EAA histidine level. Plasma AA profiles have been studied in children treated with CAPD [6,11,20]. In these studies, low values for all mean EAA levels (except phenylalanine and methionine) were reported compared with a small control group. Small discrepancies between the results of these studies exist. In our series, only serum valine was below the 3d percentile of normal age matched children. Leucine, threonine, lysine and histidine levels were below p25, isoleucine and methionine levels were above p25. We point out that in these children on NIPD, plasma EAA levels are already in the low range. The children reported in the literature with low EAA were on CAPD for a longer time. The protein and caloric intake was according to recommended dietary allowance for age. It was lower in the two teenagers and higher in the younger children. The loss of EAA with an icodextrin daytime dwell described here suggests that long-term use of daytime dwells could lead to low plasma EAA levels. Plasma NEAA were normal except for low tyrosine and high citrulline, which is generally described in all series [6,11,20]. A significant decrease in glutamine occurred, but it remained in the normal range.

It remains to be determined if EAA levels decrease below p3 with long-term daytime dwells with icodextrin. The loss of 3.5% of total protein intake should be counterbalanced by increase in protein intake. However, no spontaneous increase in dietary intake was noted in these patients. The full abdomen during daytime did not negatively affect nutritional intake either.

For safety reasons, a short observation period was preferred but we appreciate that a longer study period is needed to confirm these results. It might be that some effects need more time to become clinically detectable (change in appetite) or possibly amplify the observed differences.



   Conclusions
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
 References
 
It is possible to increase dialysis dose significantly by introducing a daytime dwell with icodextrin to a NIPD regimen in children. This increased dose does not affect albumin homeostasis or serum lipid profiles on a short term of 1 week.

The full abdomen during daytime does not affect dietary calorie and protein intake. Fluid balance is not disturbed with adequate intake.

Patients on NIPD demonstrate EAA plasma levels below p25 for age-matched controls (except for methionine). An increased amount of EAA and NEAA is lost. The effect of long-term daytime icodextrin dwell on these levels remains to be established. But, we suggest monitoring dietary intake and EAA levels every 3 months in children while increasing dialysis doses with icodextrin daytime dwell.

Conflict of interest statement. None declared.



   Notes
 
Correspondence and offprint requests to: K. J. M. Van Hoeck, Department Pediatric Nephrology, University Hospital Antwerp, Wilrijkstraat 10, B-2650 Edegem, Belgium. Email: koen.van.hoeck{at}uza.be Back



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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusions
 References
 

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Received for publication: 6. 7.02
Accepted in revised form: 17. 1.03





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