Effects of Bicarbonate/Lactate Solution on Peritoneal Advanced Glycosylation End-Product Accumulation

Abstract

Advanced glycosylation end-products (AGEs) are associated with diabetic complications and peritoneal damage after long-term peritoneal dialysis (PD) with high glucose dialysis solutions. Glucose degradation products (GDPs) derived during heat sterilization of high glucose dialysis solutions are thought to accelerate AGE formation. A new technique of separating glucose from electrolytes has yielded markedly lower GDP levels and permitted the use of dialysis solutions containing the physiologic buffer bicarbonate. Formation of AGEs in vitro with this new solution is significantly lower compared with formation of AGEs with conventional solutions. The purpose of the present study was to investigate the effect of long-term intraperitoneal use of new, neutral dialysis solution (B/L) containing bicarbonate (25 mmol/L) and lactate (15 mmol/L) on peritoneal AGE accumulation and permeability. Normal male Sprague-Dawley rats were used. Twice daily for 12 weeks, 30 mL of new solution (B/L) or conventional solution [Lac (lactate 40 mmol/L)] was injected into the peritoneal cavity of the test rats. As a control, rats that were not injected were kept for 12 weeks in the same manner as the test rats. After 12 weeks, a 2-hour peritoneal equilibration test (PET) was performed in the test rats. After the PET, the parietal peritoneum and liver were obtained for evaluation of peritoneal morphology and for immunohistochemistry for AGE. Intensity of AGE staining was semi-quantitatively graded from 0 to 3. The omentum was also obtained and immediately frozen for analysis of pentosidine content by high-performance liquid chromatography. Compared with findings in the control group, hematoxylin and eosin staining of the parietal peritoneum and liver samples revealed partial denudation of mesothelial cells in the Lac group; denudation was not remarkable in the B/L group. The B/L solution showed significantly less AGE staining in the peritoneal cavity compared to conventional solution. However, B/L solution failed to lower pentosidine levels. Intraperitoneal volume and the ratio of dialysate glucose at 2 hours to dialysate glucose at instillation (D2/D0 glucose) were significantly lower and the ratio of dialysate urea to plasma urea at 2 hours (D2/P2 urea) was significantly higher in the Lac and B/L groups than in the control group. Intraperitoneal volume was significantly higher in the B/L group than in the Lac group; D2/D glucose and D2P2 urea did not differ between the two groups. In conclusion, peritoneal ultrafiltration decreased after long-term PD. The B/L solution showed a small but statistically significant protective effect against decreasing ultrafiltration as compared with Lac solution. The B/L solution attenuated peritoneal AGE accumulation compared with conventional solution, but did not affect peritoneal pentosidine levels. These findings indicate that biochemical kinetics of various AGE peptides are not unique, but multivalent.