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Bench Science |
1 Divisions of Baxter Novum and Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden; 2 Department of Pathophysiology, Poznan Medical School, Poznan; 3 Institute of Biocybernetics and Biomedical Engineering, Warsaw, Poland
Correspondence to: B. Lindholm, K-56 Baxter Novum and Renal Medicine,
Karolinska University Hospital Huddinge, Karolinska Institutet, S-141 86
Stockholm,
Sweden.
Bengt.Lindholm{at}ki.se
Objective: To study the metabolism of icodextrin and
-amylase activity following daily exposure to dialysis solutions
containing either glucose or icodextrin as osmotic agent in rats. Methods: Male Wistar rats with implanted peritoneal
catheters were infused twice daily for 3 weeks with 20 mL 7.5%
icodextrin-based peritoneal dialysis fluid (IPDF; ICO group, n = 12)
or 3.86% glucose-based peritoneal dialysis fluid (GLU group, n = 11).
A 4-hour dwell study using 30 mL IPDF was performed on day 10 (D1) and day 21
(D2) in both the ICO and the GLU groups. Radiolabeled serum albumin (RISA) was
used as a macromolecular volume marker. Dialysate samples were collected at 3,
15, 30, 60, 90, 120, and 240 minutes. Blood samples were drawn before the
start and at the end of the dwell. Results: During all dwell studies, the dialysate
concentrations of total icodextrin decreased due to decrease in high molecular
weight (MW) fractions, whereas there was a marked increase in icodextrin low
MW metabolites. -Amylase activity increased in dialysate and decreased
in plasma. About 60% of the total icodextrin was absorbed from the peritoneal
cavity during the 4-hour dwells. Low MW icodextrin metabolites were present in
the dialysate already at 3 minutes, and maltose (G2), maltotriose (G3),
maltotetraose (G4), and maltopentaose (G5) increased progressively, reaching
maximum concentrations at 60 minutes. Maltohexaose (G6) and maltoheptaose (G7)
were also detected already at 3 minutes but did not change significantly
during the dwells. During the two 4-hour dwell studies (D1 and D2), the
concentrations of total icodextrin and icodextrin metabolites and
-amylase activity in dialysate did not differ between the ICO and GLU
groups, during either D1 or D2. No icodextrin metabolites were detected in
plasma at the end of the dwells. -Amylase activity in the dialysate
increased six- to eightfold whereas plasma -amylase activity decreased
by 21% - 26% during the two 4-hour dwells in both the ICO and the GLU groups;
there were no significant differences between the ICO and the GLU groups
during either D1 or D2. -Amylase activity in the dialysate correlated
strongly with the disappearance rate of icodextrin from the peritoneal cavity
during the 4-hour dwells, and with the concentrations of G2, G3, G6, and G7 in
dialysate. Conclusions: The decline in the dialysate concentrations
of high MW fractions and the increase in low MW metabolites of icodextrin
suggest intraperitoneal -amylase mediated the metabolism of icodextrin
and the transport of predominantly the smaller icodextrin metabolites from
dialysate. However, no icodextrin could be detected in plasma, suggesting that
it was metabolized and excreted by the kidney in these nonuremic rats. In
contrast to uremic peritoneal dialysis patients, chronic exposure to IPDF did
not seem to further affect -amylase activity or icodextrin metabolism.
The much higher -amylase activity in plasma and dialysate in rats than
in humans explains the much more rapid metabolism of icodextrin in rats
compared with peritoneal dialysis patients.
KEY WORDS: Icodextrin; icodextrin metabolism; -amylase activity.
Received 9 May 2006; accepted 7 February 2007.
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