Assessment of the effectiveness, safety, and biocompatibility of icodextrin in automated peritoneal dialysis. The Dextrin in APD in Amsterdam (DIANA) Group.
OBJECTIVE
Our study assessed the efficacy, safety, and biocompatibility of icodextrin (I) solution compared to glucose (G) solution as the daytime dwell in continuous cycling peritoneal dialysis (CCPD).


METHODS
In a randomized, open, prospective, parallel group study of two year's duration, either I or G was used for the long daytime dwell in CCPD patients.


METHODS
The study was carried out in a university hospital and teaching hospital. Established CCPD patients and patients new to the modality were both included. Clinic visits were made at three-month intervals. In all patients, clinical data were gathered; ultrafiltration (UF) was recorded; and serum, urine, and dialysate samples and effluents were collected. Peritoneal defense characteristics and mesothelial markers were determined. Every six months, peritoneal kinetics studies were performed, and serum samples for icodextrin metabolites were taken.


RESULTS
Thirty-eight patients (19 G, 19 I) started the study. The median follow-up was 16 months and 17 months respectively (range: 0.5 - 26 months and 3 - 26 months, respectively). Daytime UF volumes increased significantly (p < 0.001), and 24-hour UF tended to increase from baseline in the I group. Dialysate creatinine clearance increased non significantly in both groups over time. In I patients, serum disaccharides (maltose) concentration increased from 0.05+/-0.01 mg/mL [mean+/- standard error of mean (SEM)] at baseline, to an average concentration in the follow-up visits of 1.15+/- 0.04 mg/mL (p <0.001). At the same time, serum sodium levels decreased from 138.1 +/- 0.7 mmol/L to an average concentration in the follow-up visits of 135.9 +/- 0.8 mmol/L (p < 0.050). At 12 months, the serum sodium concentration increased to a non significant difference from baseline. Serum osmolality increased, but did not differ significantly from G users at any visit. During peritonitis (P), daytime dwell UF decreased significantly compared to non peritonitis (NP) episodes in G patients (p < 0.0 01), but remained stable in I patients. Total 24-hour UF also decreased in G patients (p < 0.001), but not in I patients. In these I patients, serum disaccharides increased from 0.05 +/- 0.01 mg/mL to 1.26 +/- 0.2 mg/mL during follow-up. During peritonitis, serum disaccharides concentration did not increase further (1.47 +/- 0.2 mg/mL, p= 0.56). Thirty P episodes occurred during follow-up: 16 in G patients and 14 in I patients (1 per 17.6 months and 1 per 21.9 months, respectively.) After one year, absolute number and percentage of effluent peritoneal macrophages (PM phi s) were significantly higher in I patients than in G patients. The difference in percentage persisted after two years. The phagocytic capacity of PM phi s decreased over time, resulting in a borderline significant difference for coagulase-negative staphylococci phagocytosis (p=0.005) and a significant difference for E. coli phagocytosis (p <0.05) in favor of I patients. PM phi oxidative metabolism, PM phi cytokine production, and effluent opsonic capacity remained stable over time with no difference between the groups. Mass transfer area coefficients (MTACs) and clearances were stable and appeared unaffected by G or I treatment. Effluent cancer antigen 125 (CA125) was stable in G users and tended to decrease in I users. Effluent interleukin-8 (IL-8), carboxy-terminal propeptide of type I procollagen (PICP ), and amino-terminal propeptide of type III procollagen (PIIINP) did not change over time and did not differ between the groups.


CONCLUSIONS
The use of I for the long daytime dwell in CCPD led to an increase in total UF of at least 261 mL per day, which was maintained over at least 24 months. During I treatment, serum I metabolites increased significantly and serum sodium concentrations decreased initially. As a result, serum osmolality increased slightly. Clinical adverse effects did not accompany these findings. The UF gain in the I patients was even higher during P, without a
Posthuma
N
N
Department of Nephrology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, The Netherlands.
ter Wee
P M
PM
Donker
A J
AJ
Oe
P L
PL
Peers
E M
EM
Verbrugh
H A
HA
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001331:Automation; D001672:Biocompatible Materials; D001692:Biological Transport; D015314:Dialysis Solutions / Q000493:pharmacokinetics*; D005260:Female; D005936:Glucans / Q000493:pharmacokinetics*; D005947:Glucose / Q000493:pharmacokinetics*; D006801:Humans; D000077607:Icodextrin; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis / Q000379:methods*; D010537:Peritoneum / Q000378:metabolism; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome
D001672:Biocompatible Materials; D015314:Dialysis Solutions; D005936:Glucans; D000077607:Icodextrin; D005947:Glucose