Effect of Icodextrin Solution on Preservation of Residual Renal Function in Patients on Peritoneal Dialysis
Status:
Completed
Trial end date:
2014-08-01
Target enrollment:
Participant gender:
Summary
Peritoneal dialysis (PD) is an established dialysis modality in patients with end stage renal
disease (ESRD). However, there is growing awareness of the deleterious effect of high glucose
content in PD solutions on the peritoneal membrane over time (1). Accordingly, development of
new solutions to minimize glucose-induced toxicity and/or containing an alternative osmotic
agent to glucose such as icodextrin and amino-acid were developed. Icodextrin is a mixture of
high molecular weight, water soluble glucose polymers isolated by fractionation of hydrolyzed
cornstarch (2). Unlike glucose which is absorbed from the peritoneal cavity primarily by
diffusion across the peritoneal capillary endothelium, its absorption occurs mainly due to
convective fluid movement out of the peritoneal cavity via the lymphatics (2). As a result,
relatively constant osmotic pressure is created by icodextrin, thus it can provide sustained
ultrafiltration during the long dwell.
A number of studies have reported that icodextrin-based solution provides various clinical
benefits compared with conventional glucose-based solutions (3-7). In particular, icodextrin
has been successfully used in the fluid management of PD patients (4-5, 7). However,
excessive ultrafiltration may induce underhydration, resulting in faster decline in residual
renal function. This concern was first raised by Konings et al (8). In this study, a greater
fall in residual glomerular filtration rate (GFR) was observed in patients using icodextrin
compared to those using 1.36% glucose solution. In contrast, contradictory findings were also
reported from the two studies indicating that residual renal function can be preserved by
icodextrin solution (4, 9). Although the mechanisms are not clear, possible explanation
includes the presence of high-molecular-weight icodextrin metabolites in plasma, which in
turn may increase plasma oncotic pressure and hence preserve plasma volume and renal
perfusion as suggested by Davies et al (10). Such discrepant findings may be explained by
differences in study design, baseline fluid status, and other factors affecting residual
renal function during the study. In the study by Konings et al (8), the comparative solution
was 1.36% glucose, whereas 2.27% glucose was used in the study by Davies et al (4).
Therefore, it can be speculated that volume status might differ depending on different
concentration of glucose solution, thus leading to conflicting results. Also, these two prior
studies are limited by residual renal function as secondary outcome, a short follow-up
duration (4 mo vs. 6 mo), and small number of patients (32 vs. 50).
To further explore the effects of icodextrin solution on residual renal function, the
investigators will conduct a multicenter prospective randomized controlled open-label trial.
Briefly, incident or prevalent adult CAPD patients with residual urine volume > 750 ml will
be included. Patients on APD will be excluded. After a 4-week screening period, patients will
be randomly assigned to icodextrin or 2.5% glucose solution for the long dwell. Residual GFR
and fluid status will be assessed at baseline, 6, and 12 months. Residual GFR will be
calculated as an average of urea and creatinine clearance from a 24-hour urine collection. To
assess fluid status, the investigators will use three different assessment tools; 1)
echocardiography for measuring intra vena cava (IVC) diameter and left ventricular end
diastolic diameter, 2) measurement of plasma atrial natriuretic peptide, 3) bioimpedence
analysis. Primary outcome is residual GFR change at 1-year and secondary outcome is change of
fluid status during the study period. Also, biochemical laboratory data such as hemoglobin,
hsCRP, plasma osmolality, and lipid profile, peritoneal equilibration test, dialysis
adequacy, and daily peritoneal glucose exposure will be monitored. At least 50 subjects (a
total of 100) would be required for each group to detect 50% difference of residual GFR
between the two groups if type I error rate is 5% and type II error is 20% given 30% of
drop-out rate during the study period.
Preservation of residual renal function is of paramount importance because it is an
independent risk factor of mortality in PD patients. In addition, achievement of adequate
ultrafiltration is another crucial therapeutic goal to improve clinical outcomes in these
patients. In this regard, if these two goals can be accomplished by icodextrin, it would be
an ideal dialysis solution in PD practice. The investigators study will address this issue to
answer the unresolved question on the effect of icodextrin on residual renal function."