Assessment of the effectiveness, safety, and biocompatibility of icodextrin in automated peritoneal dialysis

Objective: Our study assessed the efficacy, safety, and biocompatibility of icodextrin (I) solution compared to glucose (G) solution as the daytime dw ell in continuous cycling peritoneal dialysis (CCPD). Design: In a randomized, open, prospective, parallel group study of two yea rs' duration, either I or G was used for the long daytime dwell in CCPD pat ients. Method:The study was carried out in a university hospital and teaching hosp ital. 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 def ense characteristics and mesothelial markers were determined. Every six mon ths, peritoneal kinetics studies were performed, and serum samples for icod extrin metabolites were taken. Results: Thirty-eight patients (19 G, 19 1) started the study. The median f ollow-up was 16 months and 17 months respectively (range: 0.5 - 26 months a nd 3 - 26 months, respectively). Daytime UF volumes increased significantly (p < 0.001), and 24-hour UF tended to increase from baseline in the I grou p. Dialysate creatinine clearance increased non significantly in both group s over time. In I patients, serum disaccharides (maltose) concentration inc reased from 0.05 +/- 0.01 mg/mL [mean +/- standard error of mean (SEM)I 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 o f 135.9 +/- 0.8 mmol/L (p < 0.05). At 12 months, the serum sodium concentra tion increased to a non significant difference from baseline. Serum osmolal ity increased, but did not differ significantly from G users at any visit. During peritonitis (P), daytime dwell UF decreased significantly compared t o non peritonitis (NP) episodes in G patients (p < 0.001), but remained sta ble 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 increase d from 0.05 +/- 0.01 mg/mL to 1.26 +/- 0.2 mg/mL during follow-up. During p eritonitis, serum disaccharides concentration did not increase further (1.4 7 +/- 0.2 mg/mL, p = 0.56). Thirty P episodes occurred during follow-up: 16 in G patients and 14 in 1 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(Ps) were significantly higher in I patients tha n in G patients. The difference in percentage persisted after two years. Th e phagocytic capacity of PM Phi s decreased over time, resulting in a borde rline significant difference for coagulase-negative staphylococci phagocyto sis (p = 0.05) and a significant difference for E. coil phagocytosis (p < 0 .05) in favor of I patients. PM Phi oxidative metabolism, PM Phi cytokine p roduction, 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. Effluen t cancer antigen 125 (CA125) was stable in G users and tended to decrease i n I users. Effluent interleukin-8 (IL-8), carboxy-terminal propeptide of ty pe I procollagen (PICP), and amino-terminal propeptide of type III procolla gen (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 incr ease in total UF of at least 261 mt per day, which was maintained over at l east 24 months. During I treatment, serum I metabolites increased significa ntly and serum sodium concentrations decreased initially. As a result, seru m osmolality increased slightly. Clinical adverse effects did not accompany these findings. The UF gain in the I patients was even higher during P,wit hout a further increase in serum I metabolites. CCPD patients using I did e qually well as G-treated patients with regard to clinical infections and mo st peritoneal defense characteristics. However, in a few peritoneal defense tests, I-treated patients did better. Peritoneal transport variables did n ot change over time. Peritoneal membrane markers did not change throughout the study and did not differ between the groups.