In vitro formation of advanced glycation end products in peritoneal dialysis fluid

Abstract

Glycation of proteins in the peritoneum might occur due to the extremely high glucose concentrations (75 to 214 mmol/liter) in the dialysate of patients on continuous ambulatory peritoneal dialysis (CAPD) and may be involved in the etiology of ultrafiltration failure. Formation of both early (glycated albumin) and late (advanced glycation end products; AGE, measured as protein-derived fluorescence intensity, FI) Maillard reaction products was studied in vitro in dialysis fluids obtained from seven patients on CAPD and in phosphate buffered saline (PBS) controls paired for glucose and albumin concentrations. Percentage glycated albumin (median, range) increased (P < 0.02) from baseline after 10 and 21 days in both dialysate and PBS but did not differ (P > 0.05) between the two media at any time point (day 0, 3.6, 3.1-4.5 vs. 4.1, 3.0-4.6; day 10, 19.4, 7.9-54.8 vs. 19.1, 8.7-50.1; day 21, 29.0, 12.0-75.6 vs. 30.0, 11.7-69.8). Glycated albumin formation was linearly related to the glucose concentration (r > 0.98, P < 0.001) in both dialysate and PBS at 10 and 21 days. FI (U/g/liter albumin, median, range) increased (P < 0.02) from baseline after 10 and 21 days in dialysate but only after 21 days in PBS; this increase was significantly greater (P < 0.02) in dialysate than in PBS after 10 and 21 days (day 0, 41, 36-46 vs. 42, 37-46; day 10, 99, 88-161 vs. 51, 34-68; day 21, 113, 102-239 vs. 68, 54-91). After 21 days, FI was significantly related to glucose concentration (r = 0.90, P < 0.01) and to % glycated albumin (r = 0.92, P < 0.01) in PBS but not in dialysate (P > 0.05). AGE formation, but not glycation, decreased as a function of the dialysate dwell time and was inhibited by aminoguanidine. Our results demonstrate that formation of AGE products occurs in dialysis fluid and that factors in dialysate can modulate this process.