Advanced Glycosylation End-Products in Diabetic Rats on Peritoneal Dialysis Using Various Solutions

Abstract

To evaluate and compare the effects of glucose-based solutions to those of icodextrin with respect to peritoneal transport characteristics and advanced glycosylation end-product (AGE) formation in the peritoneal membrane in a diabetic rat model of peritoneal dialysis (PD). Thirty-three male Sprague-Dawley rats weighing between 275-300 g were divided into five groups: group C (n = 6), control rats implanted with a catheter but not dialyzed; group D (n = 5), diabetic rats implanted with a catheter but not dialyzed; group G (n = 7), diabetic rats implanted with a catheter and dialyzed with standard 2.5% glucose solution for daytime exchanges and 4.25% glucose solution for overnight exchanges; group H (n = 8), diabetic rats implanted with a catheter and dialyzed with standard 2.5% glucose solution for daytime exchanges and 7.5% icodextrin solution for overnight exchanges; group I (n = 7), diabetic rats implanted with a catheter and dialyzed with 7.5% icodextrin solution for all exchanges. Dialysis exchanges (25 mL per exchange) were performed three times daily for a period of 12 weeks. Tissue sections were stained using a monoclonal anti-AGE antibody. One-hour peritoneal equilibration tests (PET) were performed every 4 weeks for comparison of transport characteristics. The level of immunostaining was lowest in group C and highest in group G. Significant differences in immunostaining were seen between group C and group G (p < 0.001), group C and group H (p = 0.001), and group C and group I (p < 0.05). Significant differences were also found between group G and group D (p < 0.05), and between group G and group I (p < 0.05). Over time, the ratio of glucose concentration after 1 hour to glucose concentration at instillation (D/D0) decreased and the dialysate-to-plasma ratio (D/P) of urea increased. Significant differences in D/D0 glucose and D/P urea were found between group C and group H (D/D0: 0.40 +/- 0.01 vs 0.35 +/- 0.01, p < 0.05; D/P urea: 0.87 +/- 0.03 vs 0.97 +/- 0.02, p < 0.05). These results suggest that AGE formation is lower with the use of peritoneal dialysis solution containing icodextrin than with glucose-based solution. We conclude that use of icodextrin may help to slow the deterioration of the peritoneal membrane, prolonging its use for dialysis.