Icodextrin metabolism in peritoneal dialysis : clinical and experimental studies
Author: Garcia Lopez, Elvia
Date: 2007-11-09
Location: Föreläsningssalen 4U, Alfred Nobels allé 8, Karolinska Universitetssjukhuset, Huddinge
Time: 10.00
Department: Institutionen för klinisk vetenskap / Department of Clinical Sciences
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thesis.pdf (354.9Kb)
Abstract
Icodextrin is a glucose polymer which is used as osmotic agent to provide
sustained ultrafiltration (UF) during the long (8-16 hours) dwell in
end-stage renal disease patients undergoing peritoneal dialysis (PD). The
aims of this thesis were to study: the metabolism of icodextrin in the
peritoneal cavity and in the circulation of PD patients and non-uremic
rats, the role of alpha-amylase in its hydrolysis, and the rate of
breakdown of a synthetic maltoheptaose (G7) ex vivo which we propose as a
novel measure of amylase mediated oligosaccharide metabolism.
Study I. Gel-filtration HPLC was applied to determine high and low molecular weight icodextrin molecules in dialysate and plasma from PD patients using glucose solution or icodextrin (after the first dwell or chronically). Total hydrolysis of the samples was used to validate the results. 39 % of the infused icodextrin was absorbed from the peritoneal cavity during the long dwell. The plasma concentration of icodextrin metabolites was significantly higher and alpha-amylase activity significantly lower in the icodextrin groups.
Study II. An assay for measurement of total alpha-amylase activity in serum containing icodextrin degradation products was validated. The study demonstrated that the low values of plasma alpha-amylase activity in PD patients using icodextrin are correctly determined.
Study III. In 23 non-uremic rats undergoing chronic PD using either glucose- or icodextrinbased dialysis solutions, a 4-hour dwell with icodextrin was performed twice, at days 10 and 21. There was a significant decrease in amylase activity in plasma (which is much higher than in humans) and an increase in dialysate. About 60 % of the infused icodextrin was absorbed from the peritoneal cavity at the end of the dwell. No icodextrin metabolites were detected in plasma at the end of the dwell.
Study IV. The rate of degradation of G7 in plasma from healthy controls, and PD patients using only glucose solution or glucose in combination with icodextrin was investigated ex vivo. Samples were spiked with G7 and/or synthetic amylase, and incubated 4 hours at 37oC. The G7 degradation rate was lower in plasma from icodextrin patients but it was also reduced in PD patients using glucose, in spite of the higher amylase activity, as compared with the controls. This suggests that the amylase mediated carbohydrate metabolism is reduced in PD patients. It is possible that this could contribute to reduced hyperglycemic changes, especially in patients using icodextrin.
Study V. When investigating also pre-dialysis (PreD) and hemodialysis (HD) patients, we found that the rate of degradation of G7 did not differ from the controls. Amylase activity was increased in the PreD, HD and GLU patients, and decreased in the ICO patients. The rate of G7 degradation per unit of amylase activity was reduced in PreD and GLU patients. The rate of G7 degradation was related to the endogenous amylase activity. These findings suggest that the amylase mediated oligosaccharide metabolism is altered in uremic patients, although this needs to be confirmed in larger studies.
Study VI. The relationship between the efficacy of icodextrin in changing UF, fluid status and residual urine volume versus the concentration of plasma icodextrin metabolites was investigated. There was no relationship between plasma concentrations of icodextrin metabolites and any of the other clinical parameters, including change in daily UF, urine volume, fluid or inflammatory status. Icodextrin was not associated with a greater fall in urine output despite its larger effect on the volume of extra-cellular fluid.
Study I. Gel-filtration HPLC was applied to determine high and low molecular weight icodextrin molecules in dialysate and plasma from PD patients using glucose solution or icodextrin (after the first dwell or chronically). Total hydrolysis of the samples was used to validate the results. 39 % of the infused icodextrin was absorbed from the peritoneal cavity during the long dwell. The plasma concentration of icodextrin metabolites was significantly higher and alpha-amylase activity significantly lower in the icodextrin groups.
Study II. An assay for measurement of total alpha-amylase activity in serum containing icodextrin degradation products was validated. The study demonstrated that the low values of plasma alpha-amylase activity in PD patients using icodextrin are correctly determined.
Study III. In 23 non-uremic rats undergoing chronic PD using either glucose- or icodextrinbased dialysis solutions, a 4-hour dwell with icodextrin was performed twice, at days 10 and 21. There was a significant decrease in amylase activity in plasma (which is much higher than in humans) and an increase in dialysate. About 60 % of the infused icodextrin was absorbed from the peritoneal cavity at the end of the dwell. No icodextrin metabolites were detected in plasma at the end of the dwell.
Study IV. The rate of degradation of G7 in plasma from healthy controls, and PD patients using only glucose solution or glucose in combination with icodextrin was investigated ex vivo. Samples were spiked with G7 and/or synthetic amylase, and incubated 4 hours at 37oC. The G7 degradation rate was lower in plasma from icodextrin patients but it was also reduced in PD patients using glucose, in spite of the higher amylase activity, as compared with the controls. This suggests that the amylase mediated carbohydrate metabolism is reduced in PD patients. It is possible that this could contribute to reduced hyperglycemic changes, especially in patients using icodextrin.
Study V. When investigating also pre-dialysis (PreD) and hemodialysis (HD) patients, we found that the rate of degradation of G7 did not differ from the controls. Amylase activity was increased in the PreD, HD and GLU patients, and decreased in the ICO patients. The rate of G7 degradation per unit of amylase activity was reduced in PreD and GLU patients. The rate of G7 degradation was related to the endogenous amylase activity. These findings suggest that the amylase mediated oligosaccharide metabolism is altered in uremic patients, although this needs to be confirmed in larger studies.
Study VI. The relationship between the efficacy of icodextrin in changing UF, fluid status and residual urine volume versus the concentration of plasma icodextrin metabolites was investigated. There was no relationship between plasma concentrations of icodextrin metabolites and any of the other clinical parameters, including change in daily UF, urine volume, fluid or inflammatory status. Icodextrin was not associated with a greater fall in urine output despite its larger effect on the volume of extra-cellular fluid.
List of papers:
I. García-López E, Anderstam B, Heimbürger O, Amici G, Werynski A, Lindholm B (2005). "Determination of high and low molecular weight molecules of icodextrin in plasma and dialysate, using gel filtration chromatography, in peritoneal dialysis patients." Perit Dial Int 25(2): 181-91
Pubmed
II. Anderstam B, García-López E, Heimbürger O, Lindholm B (2003). "Determination of alpha-amylase activity in serum and dialysate from patients using icodextrin-based peritoneal dialysis fluid." Perit Dial Int 23(2): 146-50
Pubmed
III. García-López E, Pawlaczyk K, Anderstam B, Qureshi AR, Kuzlan-Pawlaczyk M, Heimbürger O, Werynski A, Lindholm B (1970). "Icodextrin metabolism and alpha-amylase activity in nonuremic rats undergoing chronic peritoneal dialysis." Perit Dial Int 27(4): 415-23
Pubmed
IV. Garcia-López E, Werynski A, Heimbürger O, Divino Filho JC, Lindholm B, Anderstam B (2007). "Rate of synthetic oligosaccharide degradation as a novel measure of amylase activity in peritoneal dialysis patients" Perit Dial Int, (Submitted)
V. Garcia-López E, Anderstam B, Heimbürger O, Rashid Qureshi A, Suliman ME, Bragfors-Helin AC, Stenvinkel P, Barany P, Werynski A, Divino Filho JC, Lindholm B (2007). "Abnormal amylase mediated degradation rate of maltoheptaose (G7) in endstage renal disease patients." Nephrol Dial Transplant, (Submitted)
VI. Davies SJ, Garcia-López E, Woodrow G, Donovan K, Plum J, Williams P, Johansson AC, Bosselman HP, Heimbürger O, Simonsen O, Davenport A, Lindholm B, Tranaeus A, Divino Filho JC (2007). "Longitudinal relationships between fluid status, inflammation, urine volume and plasma metabolites of icodextrin in peritoneal dialysis patients randomised double-blind to glucose or icodextrin for the long exchange." Nephrol Dial Transplant (Submitted)
I. García-López E, Anderstam B, Heimbürger O, Amici G, Werynski A, Lindholm B (2005). "Determination of high and low molecular weight molecules of icodextrin in plasma and dialysate, using gel filtration chromatography, in peritoneal dialysis patients." Perit Dial Int 25(2): 181-91
Pubmed
II. Anderstam B, García-López E, Heimbürger O, Lindholm B (2003). "Determination of alpha-amylase activity in serum and dialysate from patients using icodextrin-based peritoneal dialysis fluid." Perit Dial Int 23(2): 146-50
Pubmed
III. García-López E, Pawlaczyk K, Anderstam B, Qureshi AR, Kuzlan-Pawlaczyk M, Heimbürger O, Werynski A, Lindholm B (1970). "Icodextrin metabolism and alpha-amylase activity in nonuremic rats undergoing chronic peritoneal dialysis." Perit Dial Int 27(4): 415-23
Pubmed
IV. Garcia-López E, Werynski A, Heimbürger O, Divino Filho JC, Lindholm B, Anderstam B (2007). "Rate of synthetic oligosaccharide degradation as a novel measure of amylase activity in peritoneal dialysis patients" Perit Dial Int, (Submitted)
V. Garcia-López E, Anderstam B, Heimbürger O, Rashid Qureshi A, Suliman ME, Bragfors-Helin AC, Stenvinkel P, Barany P, Werynski A, Divino Filho JC, Lindholm B (2007). "Abnormal amylase mediated degradation rate of maltoheptaose (G7) in endstage renal disease patients." Nephrol Dial Transplant, (Submitted)
VI. Davies SJ, Garcia-López E, Woodrow G, Donovan K, Plum J, Williams P, Johansson AC, Bosselman HP, Heimbürger O, Simonsen O, Davenport A, Lindholm B, Tranaeus A, Divino Filho JC (2007). "Longitudinal relationships between fluid status, inflammation, urine volume and plasma metabolites of icodextrin in peritoneal dialysis patients randomised double-blind to glucose or icodextrin for the long exchange." Nephrol Dial Transplant (Submitted)
Issue date: 2007-10-19
Rights:
Publication year: 2007
ISBN: 978-91-7357-352-8
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