Icodextrin metabolism and alpha-amylase activity in nonuremic rats undergoing chronic peritoneal dialysis.
OBJECTIVE
To study the metabolism of icodextrin and alpha-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. alpha-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 alpha-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. alpha-Amylase activity in the dialysate increased six- to eightfold whereas plasma alpha-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. alpha-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 alpha-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 alpha-amylase activity or icodextrin metabolism. The much higher alpha-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.
García-López
Elvia
E
Divisions of Baxter Novum and Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
Pawlaczyk
Krzysztof
K
Anderstam
Björn
B
Qureshi
A Rashid
AR
Kuzlan-Pawlaczyk
Malgorzata
M
Heimbürger
Olof
O
Werynski
Andrzej
A
Lindholm
Bengt
B
D000818:Animals; D015314:Dialysis Solutions / Q000737:chemistry / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D005936:Glucans / Q000493:pharmacokinetics*; D005947:Glucose / Q000493:pharmacokinetics*; D015312:Hemodialysis Solutions; D000077607:Icodextrin; D008297:Male; D010530:Peritoneal Dialysis / Q000379:methods*; D010537:Peritoneum / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000516:alpha-Amylases / Q000097:blood / Q000378:metabolism*
D015314:Dialysis Solutions; D005936:Glucans; D015312:Hemodialysis Solutions; D000077607:Icodextrin; D000516:alpha-Amylases; D005947:Glucose