Peritoneal accumulation of AGE and peritoneal membrane permeability

In continuous ambulatory peritoneal dialysis (CAPD), the peritoneal membrane is continuously exposed to high-glucose-containing dialysis solutions. Abnormally high glucose concentration in the peritoneal cavity may enhance advanced glycosylation end-product (AGE) formation and accumulation in the peritoneum. Increased AGE accumulation in the peritoneum, decreased ultrafiltration volume, and increased peritoneal permeability in long-term dialysis patients have been reported.

The purpose of the study was to evaluate the relation between peritoneal membrane permeability and peritoneal accumulation of AGE.

Peritoneal membrane permeability was evaluated by peritoneal equilibration test (PET) using dialysis solutions containing 4.25% glucose. Serum, dialysate, and peritoneal tissue levels of AGE were measured by ELISA method using polyclonal anti-AGE antibody. Peritoneal biopsy was performed during peritoneal catheter insertion [new group (group N), n = 18] and removal [long-term group (group LT), n = 10]. Peritoneal catheters were removed due to exit-site infection not extended into the internal cuff (n = 6) and ultrafiltration failure (n = 4) after 51.6+/-31.5 months (13 - 101 months) of dialysis. PET data obtained within 3 months after the initiation of CAPD or before catheter removal were included in this study. Ten patients in group N and 4 patients in group LT were diabetic. Patients in group LT were significantly younger (46.5+/-11.1 years vs 57.5+/-1.3 years) and experienced more episodes of peritonitis (3.5+/-2.1 vs 0.2+/-0.7) than group N.

Peritoneal tissue AGE level in group LT was significantly higher than in group N, in both nondiabetic (0.187+/-0.108 U/mg vs 0.093+/-0.08 U/mg of hydroxyproline, p < 0.03) and diabetic patients (0.384+/-0.035 U/mg vs 0.152+/-0.082 U/mg of hydroxyproline, p < 0.03), while serum and dialysate levels did not differ between the groups in both nondiabetic and diabetic patients. Drain volume (2600+/-237 mL vs 2766+/-222 mL, p = 0.07) and D4/D0 glucose (0.229+/-0.066 vs 0.298+/-0.081, p < 0.009) were lower, and D4/P4 creatinine (0.807+/-0.100 vs 0.653+/-0.144, p< 0.0001) and D1/P1 sodium (0.886+/-0.040 vs 0.822+/-0.032, p < 0.0003) were significantly higher in group LT than in group N. On linear regression analysis, AGE level in the peritoneum was directly correlated with duration of CAPD (r = 0.476, p = 0.012), number of peritonitis episodes (r = 0.433, p = 0.0215), D4/P4 creatinine (r = 0.546, p < 0.027), and D1/P1 sodium (r = 0.422, p = 0.0254), and inversely correlated with drain volume (r = 0.432, p = 0.022) and D4/D0 glucose (r = 0.552, p < 0.0023). AGE level in the peritoneal tissue and dialysate were significantly higher in diabetics than in nondiabetics in group LT, while these differences were not found in group N. Serum AGE level did not differ between nondiabetics and diabetics in either group N or group LT. Drain volume and D4/D0 glucose were lower and D4/P4 creatinine and D1/P1 sodium higher in diabetics than in nondiabetics in both groups.

Peritoneal accumulation of AGE increased with time on CAPD and number of peritonitis episodes, and was directly related with peritoneal permeability. Peritoneal AGE accumulation and peritoneal permeability in diabetic patients were higher than in nondiabetic patients from the beginning of CAPD.